Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Publication Date: 2011-02-19
    Description: Toll-like receptors (TLRs) function as initiators of inflammation through their ability to sense pathogen-associated molecular patterns and products of tissue damage. Transcriptional activation of many TLR-responsive genes requires an initial de-repression step in which nuclear receptor co-repressor (NCoR) complexes are actively removed from the promoters of target genes to relieve basal repression. Ligand-dependent SUMOylation of liver X receptors (LXRs) has been found to suppress TLR4-induced transcription potently by preventing the NCoR clearance step, but the underlying mechanisms remain enigmatic. Here we provide evidence that coronin 2A (CORO2A), a component of the NCoR complex of previously unknown function, mediates TLR-induced NCoR turnover by a mechanism involving interaction with oligomeric nuclear actin. SUMOylated LXRs block NCoR turnover by binding to a conserved SUMO2/SUMO3-interaction motif in CORO2A and preventing actin recruitment. Intriguingly, the LXR transrepression pathway can itself be inactivated by inflammatory signals that induce calcium/calmodulin-dependent protein kinase IIgamma (CaMKIIgamma)-dependent phosphorylation of LXRs, leading to their deSUMOylation by the SUMO protease SENP3 and release from CORO2A. These findings uncover a CORO2A-actin-dependent mechanism for the de-repression of inflammatory response genes that can be differentially regulated by phosphorylation and by nuclear receptor signalling pathways that control immunity and homeostasis.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3464905/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3464905/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Huang, Wendy -- Ghisletti, Serena -- Saijo, Kaoru -- Gandhi, Meghal -- Aouadi, Myriam -- Tesz, Greg J -- Zhang, Dawn X -- Yao, Joyee -- Czech, Michael P -- Goode, Bruce L -- Rosenfeld, Michael G -- Glass, Christopher K -- 1F31DK083913/DK/NIDDK NIH HHS/ -- CA52599/CA/NCI NIH HHS/ -- DK074868/DK/NIDDK NIH HHS/ -- DK085853/DK/NIDDK NIH HHS/ -- HC088093/HC/NHLBI NIH HHS/ -- P01 DK074868/DK/NIDDK NIH HHS/ -- P50 HL056989/HL/NHLBI NIH HHS/ -- R01 CA052599/CA/NCI NIH HHS/ -- R01 CA097134/CA/NCI NIH HHS/ -- R01 DK091183/DK/NIDDK NIH HHS/ -- R01 HL065445/HL/NHLBI NIH HHS/ -- R01 NS034934/NS/NINDS NIH HHS/ -- R37 DK039949/DK/NIDDK NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2011 Feb 17;470(7334):414-8. doi: 10.1038/nature09703.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cellular and Molecular Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093-0651, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21331046" target="_blank"〉PubMed〈/a〉
    Keywords: Actins/chemistry/*metabolism ; Animals ; Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism ; Cell Line ; *Gene Expression Regulation/drug effects ; Gene Knockdown Techniques ; HeLa Cells ; Homeostasis/genetics ; Humans ; Inflammation/*genetics ; Lipopolysaccharides/pharmacology ; Mice ; Microfilament Proteins/chemistry/deficiency/genetics/*metabolism ; Orphan Nuclear Receptors/metabolism ; Peptide Hydrolases/metabolism ; Peritonitis/chemically induced/metabolism ; Phosphorylation ; Promoter Regions, Genetic/genetics ; Protein Structure, Tertiary ; Signal Transduction ; Sumoylation ; Thioglycolates/pharmacology ; Toll-Like Receptors/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Signatur Availability
    BibTip Others were also interested in ...
  • 2
    Publication Date: 2012-03-31
    Description: The circadian clock acts at the genomic level to coordinate internal behavioural and physiological rhythms via the CLOCK-BMAL1 transcriptional heterodimer. Although the nuclear receptors REV-ERB-alpha and REV-ERB-beta have been proposed to form an accessory feedback loop that contributes to clock function, their precise roles and importance remain unresolved. To establish their regulatory potential, we determined the genome-wide cis-acting targets (cistromes) of both REV-ERB isoforms in murine liver, which revealed shared recognition at over 50% of their total DNA binding sites and extensive overlap with the master circadian regulator BMAL1. Although REV-ERB-alpha has been shown to regulate Bmal1 expression directly, our cistromic analysis reveals a more profound connection between BMAL1 and the REV-ERB-alpha and REV-ERB-beta genomic regulatory circuits than was previously suspected. Genes within the intersection of the BMAL1, REV-ERB-alpha and REV-ERB-beta cistromes are highly enriched for both clock and metabolic functions. As predicted by the cistromic analysis, dual depletion of Rev-erb-alpha and Rev-erb-beta function by creating double-knockout mice profoundly disrupted circadian expression of core circadian clock and lipid homeostatic gene networks. As a result, double-knockout mice show markedly altered circadian wheel-running behaviour and deregulated lipid metabolism. These data now unite REV-ERB-alpha and REV-ERB-beta with PER, CRY and other components of the principal feedback loop that drives circadian expression and indicate a more integral mechanism for the coordination of circadian rhythm and metabolism.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3367514/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3367514/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cho, Han -- Zhao, Xuan -- Hatori, Megumi -- Yu, Ruth T -- Barish, Grant D -- Lam, Michael T -- Chong, Ling-Wa -- DiTacchio, Luciano -- Atkins, Annette R -- Glass, Christopher K -- Liddle, Christopher -- Auwerx, Johan -- Downes, Michael -- Panda, Satchidananda -- Evans, Ronald M -- DK057978/DK/NIDDK NIH HHS/ -- DK062434/DK/NIDDK NIH HHS/ -- DK090962/DK/NIDDK NIH HHS/ -- DK091618/DK/NIDDK NIH HHS/ -- HL105278/HL/NHLBI NIH HHS/ -- P30 CA014195/CA/NCI NIH HHS/ -- R01 DK091618/DK/NIDDK NIH HHS/ -- R01 HL105278/HL/NHLBI NIH HHS/ -- R01 HL105278-21/HL/NHLBI NIH HHS/ -- R24 DK090962/DK/NIDDK NIH HHS/ -- R24 DK090962-02/DK/NIDDK NIH HHS/ -- R37 DK057978/DK/NIDDK NIH HHS/ -- R37 DK057978-34/DK/NIDDK NIH HHS/ -- T32 HL007770/HL/NHLBI NIH HHS/ -- T32 HL007770-15/HL/NHLBI NIH HHS/ -- T32-HL007770/HL/NHLBI NIH HHS/ -- U19 DK062434/DK/NIDDK NIH HHS/ -- U19 DK062434-10/DK/NIDDK NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2012 Mar 29;485(7396):123-7. doi: 10.1038/nature11048.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, California 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22460952" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biological Clocks/drug effects/genetics ; Circadian Rhythm/genetics/*physiology ; Cryptochromes/deficiency/genetics/metabolism ; *Energy Metabolism/genetics ; Feedback, Physiological ; Gene Expression Regulation ; Gene Regulatory Networks/genetics ; Homeostasis/genetics ; *Lipid Metabolism/genetics ; Liver/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Molecular Sequence Data ; Motor Activity/genetics/physiology ; Nuclear Receptor Subfamily 1, Group D, Member 1/deficiency/genetics/*metabolism ; Period Circadian Proteins/deficiency/genetics/metabolism ; Receptors, Cytoplasmic and Nuclear/deficiency/genetics/*metabolism ; Repressor Proteins/deficiency/genetics/*metabolism ; Transcriptome/genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Signatur Availability
    BibTip Others were also interested in ...
  • 3
    Publication Date: 2013-10-15
    Description: The mechanisms by which genetic variation affects transcription regulation and phenotypes at the nucleotide level are incompletely understood. Here we use natural genetic variation as an in vivo mutagenesis screen to assess the genome-wide effects of sequence variation on lineage-determining and signal-specific transcription factor binding, epigenomics and transcriptional outcomes in primary macrophages from different mouse strains. We find substantial genetic evidence to support the concept that lineage-determining transcription factors define epigenetic and transcriptomic states by selecting enhancer-like regions in the genome in a collaborative fashion and facilitating binding of signal-dependent factors. This hierarchical model of transcription factor function suggests that limited sets of genomic data for lineage-determining transcription factors and informative histone modifications can be used for the prioritization of disease-associated regulatory variants.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3994126/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3994126/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Heinz, S -- Romanoski, C E -- Benner, C -- Allison, K A -- Kaikkonen, M U -- Orozco, L D -- Glass, C K -- 5T32DK007494/DK/NIDDK NIH HHS/ -- CA17390/CA/NCI NIH HHS/ -- DK063491/DK/NIDDK NIH HHS/ -- DK091183/DK/NIDDK NIH HHS/ -- P01 DK074868/DK/NIDDK NIH HHS/ -- P30 CA023100/CA/NCI NIH HHS/ -- P30 DK063491/DK/NIDDK NIH HHS/ -- R01 CA173903/CA/NCI NIH HHS/ -- R01 DK091183/DK/NIDDK NIH HHS/ -- T32 AR059033/AR/NIAMS NIH HHS/ -- England -- Nature. 2013 Nov 28;503(7477):487-92. doi: 10.1038/nature12615. Epub 2013 Oct 13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Cellular and Molecular Medicine, University of California, San Diego, 9500 Gilman Drive, Mail Code 0651, La Jolla, California 92093, USA [2].〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24121437" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Motifs/genetics ; Animals ; Base Sequence ; Cell Lineage/genetics ; DNA-Binding Proteins/metabolism ; Enhancer Elements, Genetic/*genetics ; Gene Expression Regulation/*genetics ; Genetic Variation/*genetics ; Histones/chemistry/metabolism ; Macrophages/metabolism ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Models, Biological ; Mutation/genetics ; NF-kappa B/metabolism ; Protein Binding ; Reproducibility of Results ; Selection, Genetic/*genetics ; Transcription Factor RelA/metabolism ; Transcription Factors/*metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Signatur Availability
    BibTip Others were also interested in ...
  • 4
    Publication Date: 2015-02-20
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Romanoski, Casey E -- Glass, Christopher K -- Stunnenberg, Hendrik G -- Wilson, Laurence -- Almouzni, Genevieve -- R01 CA173903/CA/NCI NIH HHS/ -- England -- Nature. 2015 Feb 19;518(7539):314-6. doi: 10.1038/518314a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, California 92093-0651, USA. ; Department of Molecular Biology, Faculty of Sciences, Radboud University, Nijmegen 6525 GA, the Netherlands. ; Institut Curie, CNRS Unit UMR3664, 75231 Paris Cedex 05, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25693562" target="_blank"〉PubMed〈/a〉
    Keywords: Alzheimer Disease/genetics/immunology ; Autoimmune Diseases/genetics ; Cell Differentiation/genetics ; Chromatin/chemistry/genetics/metabolism ; DNA Methylation ; Enhancer Elements, Genetic/genetics ; Epigenesis, Genetic/*genetics ; *Epigenomics ; Genome, Human/genetics ; Haplotypes/genetics ; Histones/genetics/metabolism ; Humans ; Neoplasms/genetics/pathology ; Organ Specificity ; Promoter Regions, Genetic/genetics ; Transcription Factors/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Signatur Availability
    BibTip Others were also interested in ...
  • 5
    Publication Date: 2013-01-12
    Description: A number of widespread and devastating chronic diseases, including atherosclerosis, type 2 diabetes, and Alzheimer's disease, have a pathophysiologically important inflammatory component. In these diseases, the precise identity of the inflammatory stimulus is often unknown and, if known, is difficult to remove. Thus, there is interest in therapeutically targeting the inflammatory response. Although there has been success with anti-inflammatory therapy in chronic diseases triggered by primary inflammation dysregulation or autoimmunity, there are considerable limitations. In particular, the inflammatory response is critical for survival. As a result, redundancy, compensatory pathways, and necessity narrow the risk:benefit ratio of anti-inflammatory drugs. However, new advances in understanding inflammatory signaling and its links to resolution pathways, together with new drug development, offer promise in this area of translational biomedical research.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3608517/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3608517/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tabas, Ira -- Glass, Christopher K -- DK074868/DK/NIDDK NIH HHS/ -- DK091183/DK/NIDDK NIH HHS/ -- HC088093/HC/NHLBI NIH HHS/ -- P01 DK074868/DK/NIDDK NIH HHS/ -- P01 HL054591/HL/NHLBI NIH HHS/ -- P01 HL087123/HL/NHLBI NIH HHS/ -- P01-HL054591/HL/NHLBI NIH HHS/ -- R01 DK091183/DK/NIDDK NIH HHS/ -- R01 HL075662/HL/NHLBI NIH HHS/ -- R01 HL106019/HL/NHLBI NIH HHS/ -- R01 HL107497/HL/NHLBI NIH HHS/ -- R01-HL057560/HL/NHLBI NIH HHS/ -- R01-HL075662/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2013 Jan 11;339(6116):166-72. doi: 10.1126/science.1230720.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, Columbia University, New York, NY 10032, USA. iat1@columbia.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23307734" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Anti-Inflammatory Agents/*therapeutic use ; Autoimmune Diseases/*drug therapy/physiopathology ; Cardiovascular Diseases/*drug therapy/physiopathology ; Chronic Disease/*drug therapy ; Diabetes Mellitus, Type 2/*drug therapy/physiopathology ; Humans ; Inflammation/drug therapy/physiopathology ; Neurodegenerative Diseases/*drug therapy/physiopathology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Signatur Availability
    BibTip Others were also interested in ...
  • 6
    Publication Date: 2013-06-04
    Description: Rev-Erb-alpha and Rev-Erb-beta are nuclear receptors that regulate the expression of genes involved in the control of circadian rhythm, metabolism and inflammatory responses. Rev-Erbs function as transcriptional repressors by recruiting nuclear receptor co-repressor (NCoR)-HDAC3 complexes to Rev-Erb response elements in enhancers and promoters of target genes, but the molecular basis for cell-specific programs of repression is not known. Here we present evidence that in mouse macrophages Rev-Erbs regulate target gene expression by inhibiting the functions of distal enhancers that are selected by macrophage-lineage-determining factors, thereby establishing a macrophage-specific program of repression. Remarkably, the repressive functions of Rev-Erbs are associated with their ability to inhibit the transcription of enhancer-derived RNAs (eRNAs). Furthermore, targeted degradation of eRNAs at two enhancers subject to negative regulation by Rev-Erbs resulted in reduced expression of nearby messenger RNAs, suggesting a direct role of these eRNAs in enhancer function. By precisely defining eRNA start sites using a modified form of global run-on sequencing that quantifies nascent 5' ends, we show that transfer of full enhancer activity to a target promoter requires both the sequences mediating transcription-factor binding and the specific sequences encoding the eRNA transcript. These studies provide evidence for a direct role of eRNAs in contributing to enhancer functions and suggest that Rev-Erbs act to suppress gene expression at a distance by repressing eRNA transcription.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3839578/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3839578/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lam, Michael T Y -- Cho, Han -- Lesch, Hanna P -- Gosselin, David -- Heinz, Sven -- Tanaka-Oishi, Yumiko -- Benner, Christopher -- Kaikkonen, Minna U -- Kim, Aneeza S -- Kosaka, Mika -- Lee, Cindy Y -- Watt, Andy -- Grossman, Tamar R -- Rosenfeld, Michael G -- Evans, Ronald M -- Glass, Christopher K -- CA014195/CA/NCI NIH HHS/ -- CA17390/CA/NCI NIH HHS/ -- CA52599/CA/NCI NIH HHS/ -- DK057978/DK/NIDDK NIH HHS/ -- DK063491/DK/NIDDK NIH HHS/ -- DK091183/DK/NIDDK NIH HHS/ -- HL088093/HL/NHLBI NIH HHS/ -- HL105278/HL/NHLBI NIH HHS/ -- P01 DK074868/DK/NIDDK NIH HHS/ -- P01 HL088093/HL/NHLBI NIH HHS/ -- P30 CA014195/CA/NCI NIH HHS/ -- P30 DK063491/DK/NIDDK NIH HHS/ -- R01 CA052599/CA/NCI NIH HHS/ -- R01 CA173903/CA/NCI NIH HHS/ -- R01 DK018477/DK/NIDDK NIH HHS/ -- R01 DK091183/DK/NIDDK NIH HHS/ -- R01 HL105278/HL/NHLBI NIH HHS/ -- R37 DK057978/DK/NIDDK NIH HHS/ -- T32 GM007198-37/GM/NIGMS NIH HHS/ -- T32 GM008666/GM/NIGMS NIH HHS/ -- U19 DK062434/DK/NIDDK NIH HHS/ -- U19DK62434/DK/NIDDK NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2013 Jun 27;498(7455):511-5. doi: 10.1038/nature12209. Epub 2013 Jun 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cellular and Molecular Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23728303" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Animals ; Base Sequence ; Binding Sites ; Down-Regulation/*genetics ; Enhancer Elements, Genetic/*genetics ; Gene Knockdown Techniques ; Macrophages/*metabolism ; Mice ; Nuclear Receptor Subfamily 1, Group D, Member 1/deficiency/genetics/*metabolism ; Organ Specificity ; Promoter Regions, Genetic/genetics ; RNA, Messenger/genetics/metabolism ; Response Elements/genetics ; Transcription, Genetic/*genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Signatur Availability
    BibTip Others were also interested in ...
  • 7
    Publication Date: 2013-06-04
    Description: The functional importance of gene enhancers in regulated gene expression is well established. In addition to widespread transcription of long non-coding RNAs (lncRNAs) in mammalian cells, bidirectional ncRNAs are transcribed on enhancers, and are thus referred to as enhancer RNAs (eRNAs). However, it has remained unclear whether these eRNAs are functional or merely a reflection of enhancer activation. Here we report that in human breast cancer cells 17beta-oestradiol (E2)-bound oestrogen receptor alpha (ER-alpha) causes a global increase in eRNA transcription on enhancers adjacent to E2-upregulated coding genes. These induced eRNAs, as functional transcripts, seem to exert important roles for the observed ligand-dependent induction of target coding genes, increasing the strength of specific enhancer-promoter looping initiated by ER-alpha binding. Cohesin, present on many ER-alpha-regulated enhancers even before ligand treatment, apparently contributes to E2-dependent gene activation, at least in part by stabilizing E2/ER-alpha/eRNA-induced enhancer-promoter looping. Our data indicate that eRNAs are likely to have important functions in many regulated programs of gene transcription.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3718886/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3718886/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Li, Wenbo -- Notani, Dimple -- Ma, Qi -- Tanasa, Bogdan -- Nunez, Esperanza -- Chen, Aaron Yun -- Merkurjev, Daria -- Zhang, Jie -- Ohgi, Kenneth -- Song, Xiaoyuan -- Oh, Soohwan -- Kim, Hong-Sook -- Glass, Christopher K -- Rosenfeld, Michael G -- CA173903/CA/NCI NIH HHS/ -- DK 039949/DK/NIDDK NIH HHS/ -- DK018477/DK/NIDDK NIH HHS/ -- HL065445/HL/NHLBI NIH HHS/ -- NS034934/NS/NINDS NIH HHS/ -- P30 CA023100/CA/NCI NIH HHS/ -- P30 CA23100/CA/NCI NIH HHS/ -- R01 CA097134/CA/NCI NIH HHS/ -- R01 CA173903/CA/NCI NIH HHS/ -- R01 DK018477/DK/NIDDK NIH HHS/ -- R01 DK039949/DK/NIDDK NIH HHS/ -- R01 HL065445/HL/NHLBI NIH HHS/ -- R01 NS034934/NS/NINDS NIH HHS/ -- R37 DK039949/DK/NIDDK NIH HHS/ -- T32 CA009523/CA/NCI NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2013 Jun 27;498(7455):516-20. doi: 10.1038/nature12210. Epub 2013 Jun 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Department of Medicine, School of Medicine, University of California, San Diego, La Jolla, California 92093, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23728302" target="_blank"〉PubMed〈/a〉
    Keywords: Cell Cycle Proteins/metabolism ; Chromosomal Proteins, Non-Histone/metabolism ; Enhancer Elements, Genetic/*genetics ; Estradiol/pharmacology ; Estrogen Receptor alpha/metabolism ; Estrogens/*pharmacology ; Humans ; Ligands ; MCF-7 Cells ; Nucleic Acid Conformation/drug effects ; Promoter Regions, Genetic/genetics ; RNA, Untranslated/biosynthesis/*genetics/metabolism ; Transcription, Genetic/drug effects/genetics ; Transcriptional Activation/*drug effects/genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Signatur Availability
    BibTip Others were also interested in ...
  • 8
    Publication Date: 2011-05-17
    Description: Mammalian genomes are populated with thousands of transcriptional enhancers that orchestrate cell-type-specific gene expression programs, but how those enhancers are exploited to institute alternative, signal-dependent transcriptional responses remains poorly understood. Here we present evidence that cell-lineage-specific factors, such as FoxA1, can simultaneously facilitate and restrict key regulated transcription factors, exemplified by the androgen receptor (AR), to act on structurally and functionally distinct classes of enhancer. Consequently, FoxA1 downregulation, an unfavourable prognostic sign in certain advanced prostate tumours, triggers dramatic reprogramming of the hormonal response by causing a massive switch in AR binding to a distinct cohort of pre-established enhancers. These enhancers are functional, as evidenced by the production of enhancer-templated non-coding RNA (eRNA) based on global nuclear run-on sequencing (GRO-seq) analysis, with a unique class apparently requiring no nucleosome remodelling to induce specific enhancer-promoter looping and gene activation. GRO-seq data also suggest that liganded AR induces both transcription initiation and elongation. Together, these findings reveal a large repository of active enhancers that can be dynamically tuned to elicit alternative gene expression programs, which may underlie many sequential gene expression events in development, cell differentiation and disease progression.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3117022/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3117022/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, Dong -- Garcia-Bassets, Ivan -- Benner, Chris -- Li, Wenbo -- Su, Xue -- Zhou, Yiming -- Qiu, Jinsong -- Liu, Wen -- Kaikkonen, Minna U -- Ohgi, Kenneth A -- Glass, Christopher K -- Rosenfeld, Michael G -- Fu, Xiang-Dong -- DK01847/DK/NIDDK NIH HHS/ -- DK074868/DK/NIDDK NIH HHS/ -- DK37949/DK/NIDDK NIH HHS/ -- GM049369/GM/NIGMS NIH HHS/ -- HG004659/HG/NHGRI NIH HHS/ -- NS34934/NS/NINDS NIH HHS/ -- P01 DK074868/DK/NIDDK NIH HHS/ -- P01 DK074868-05/DK/NIDDK NIH HHS/ -- P30 AG038072/AG/NIA NIH HHS/ -- R01 CA097134/CA/NCI NIH HHS/ -- R01 CA097134-10/CA/NCI NIH HHS/ -- R01 DK018477/DK/NIDDK NIH HHS/ -- R01 DK018477-35/DK/NIDDK NIH HHS/ -- R01 DK039949/DK/NIDDK NIH HHS/ -- R01 DK039949-30/DK/NIDDK NIH HHS/ -- R01 DK091183/DK/NIDDK NIH HHS/ -- R01 GM049369/GM/NIGMS NIH HHS/ -- R01 GM049369-17/GM/NIGMS NIH HHS/ -- R01 HG004659/HG/NHGRI NIH HHS/ -- R01 HG004659-03/HG/NHGRI NIH HHS/ -- R01 HL065445/HL/NHLBI NIH HHS/ -- R01 HL065445-12/HL/NHLBI NIH HHS/ -- R01 NS034934/NS/NINDS NIH HHS/ -- R01 NS034934-23/NS/NINDS NIH HHS/ -- R37 DK039949/DK/NIDDK NIH HHS/ -- R37 DK039949-28/DK/NIDDK NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2011 May 15;474(7351):390-4. doi: 10.1038/nature10006.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cellular and Molecular Medicine, School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093-0651, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21572438" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Cell Line, Tumor ; Cell Lineage ; Dihydrotestosterone/pharmacology ; Down-Regulation ; Enhancer Elements, Genetic/*genetics ; Gene Expression Regulation, Neoplastic ; Gene Knockdown Techniques ; Genome, Human/genetics ; HEK293 Cells ; Hepatocyte Nuclear Factor 3-alpha/deficiency/genetics/*metabolism ; Histones/metabolism ; Humans ; Kallikreins ; Male ; Prostate-Specific Antigen ; Prostatic Neoplasms/metabolism/pathology ; RNA, Small Interfering/genetics/metabolism ; RNA, Untranslated/*genetics ; Receptors, Androgen/*metabolism ; Transcription, Genetic/*genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Signatur Availability
    BibTip Others were also interested in ...
  • 9
    Publication Date: 2018-02-21
    Description: B-1 cells are a unique subset of B cells that are positively selected for expressing autoreactive BCRs. We isolated RNA from peritoneal (B-1a, B-1b, B-2) and splenic (B-1a, marginal zone, follicular) B cells from C57BL/6 mice and used 5'-RACE to amplify the IgH V region using massively parallel sequencing. By analyzing 379,000 functional transcripts, we demonstrate that B-1a cells use a distinct and restricted repertoire. All B-1 cell subsets, especially peritoneal B-1a cells, had a high proportion of sequences without N additions, suggesting predominantly prenatal development. Their transcripts differed markedly and uniquely contained V H 11 and V H 12 genes, which were rearranged only with a restricted selection of D and J genes, unlike other V genes. Compared to peritoneal B-1a, the peritoneal B-1b repertoire was larger, had little overlap with B-1a, and most sequences contained N additions. Similarly, the splenic B-1a repertoire differed from peritoneal B-1a sequences, having more unique sequences and more frequent N additions, suggesting influx of B-1a cells into the spleen from nonperitoneal sites. Two CDR3s, previously described as Abs to bromelain-treated RBCs, comprised 43% of peritoneal B-1a sequences. We show that a single-chain variable fragment designed after the most prevalent B-1a sequence bound oxidation-specific epitopes such as the phosphocholine of oxidized phospholipids. In summary, we provide the IgH V region library of six murine B cell subsets, including, to our knowledge for the first time, a comparison between B-1a and B-1b cells, and we highlight qualities of B-1 cell Abs that indicate unique selection processes.
    Print ISSN: 0022-1767
    Electronic ISSN: 1550-6606
    Topics: Medicine
    Signatur Availability
    BibTip Others were also interested in ...
  • 10
    Publication Date: 2018-05-26
    Description: Our understanding of transcription by RNA polymerase II (Pol II) is limited by our knowledge of the factors that mediate this critically important process. Here we describe the identification of NDF, a nucleosome-destabilizing factor that facilitates Pol II transcription in chromatin. NDF has a PWWP motif, interacts with nucleosomes near the dyad, destabilizes nucleosomes in an ATP-independent manner, and facilitates transcription by Pol II through nucleosomes in a purified and defined transcription system as well as in cell nuclei. Upon transcriptional induction, NDF is recruited to the transcribed regions of thousands of genes and colocalizes with a subset of H3K36me3-enriched regions. Notably, the recruitment of NDF to gene bodies is accompanied by an increase in the transcript levels of many of the NDF-enriched genes. In addition, the global loss of NDF results in a decrease in the RNA levels of many genes. In humans, NDF is present at high levels in all tested tissue types, is essential in stem cells, and is frequently overexpressed in breast cancer. These findings indicate that NDF is a nucleosome-destabilizing factor that is recruited to gene bodies during transcriptional activation and facilitates Pol II transcription through nucleosomes.
    Print ISSN: 0890-9369
    Topics: Biology
    Signatur Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...