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Series GSE62482 Query DataSets for GSE62482
Status Public on Jun 08, 2016
Title T-bet activates poised Th1 genes through Mediator and the Super Elongation Complex [ChIP-Seq]
Organisms Homo sapiens; Mus musculus
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary The transcription factor T-bet directs Th1 cell differentiation, but the molecular mechanisms that underlie this lineage-specific gene regulation are not completely understood. Here, we show that T-bet acts through super-enhancers in human and mouse Th1 cells to recruit Mediator and P-TEFb in the form of the super elongation complex (SEC). Th1-specific genes are poised in Th2 cells while T-bet-mediated recruitment of P-TEFb in Th1 cells activates transcriptional elongation. P-TEFb is recruited to both genes and super-enhancers, where it activates enhancer RNA transcription. P-TEFb inhibition and Mediator and SEC knockdown selectively block activation of T-bet target genes and P-TEFb inhibition abrogates Th1-associated experimental autoimmune uveitis. T-bet activity is independent of changes in NF-κB RelA and Brd4 binding, but T-bet- and NF-κB-mediated pathways converge to allow P-TEFb recruitment. These data support a model in which lineage-specifying factors allow recruitment of P-TEFb to poised genes to promote differentiation of alternative T cell fates.
 
Overall design Indentification of P-TEFb binding sites in human Th1 and Th2 cells
Indentification of RelA binding sites in human Th1 cells treated with BAY 11-7082 and DMSO control
Indentification of P-TEFb binding sites in human Th1 cells treated with BAY 11-7082 and DMSO control
Indentification of AFF4 binding sites in human Th1 cells treated with BAY 11-7082 and DMSO control
Indentification of BRD4 binding sites in human Th1 cells treated with BAY 11-7082 and DMSO control
Indentification of MED1 binding sites in human Th1 cells treated with BAY 11-7082 and DMSO control
Indentification of P-TEFb binding sites in mouse wild-type and T-bet -/- Th1 and wild-type Th2 cells
Indentification of RelA binding sites in mouse wild-type and T-bet -/- Th1 cells
Indentification of Brd4 binding sites in mouse wild-type and T-bet -/- Th1 cells
Indentification of Med1 binding sites in mouse wild-type and T-bet -/- Th1 cells
Indentification of Aff4 binding sites in mouse wild-type and T-bet -/- Th1 cells
Indentification of P-TEFb binding sites in EL4-GFP and EL4-T-bet cells
Indentification of Flag-T-bet binding sites in EL4-T-bet-mPlum and EL4-Gata3-GFP cells
Indentification of RelA binding sites in EL4-GFP and EL4-T-bet cells
Indentification of Brd4 binding sites in EL4-GFP and EL4-T-bet cells
Indentification of Med1 binding sites in EL4-GFP and EL4-T-bet cells
Indentification of Aff4 binding sites in EL4-GFP and EL4-T-bet cells
Indentification of RNA polymerase II binding sites in human Th1 and Th2 cells
Mapping of H3K4me3 histone modifications in human Th1 and Th2 cells
Mapping of H3K4me3 histone modifications in human CCR5+ memory Th1
Mapping of H3 histone in human CCR5+ memory Th1
Mapping of H3K27ac histone modifications in human Th1 and Th2 cells
Mapping of H3K4me3 histone modifications in mouse wild-type and T-bet-/- Th1 cells
Mapping of H3 histone in mouse wild-type and T-bet-/- Th1 cells
 
Contributor(s) Jenner R, Arnulf H
Citation(s) 27292648
Submission date Oct 18, 2014
Last update date May 15, 2019
Contact name Richard Jenner
E-mail(s) r.jenner@ucl.ac.uk
Organization name UCL Cancer Institute
Department Cancer Biology
Lab Regulatory Genomics
Street address 72 Huntley Street
City London
ZIP/Postal code WC1E 6BT
Country United Kingdom
 
Platforms (2)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
GPL13112 Illumina HiSeq 2000 (Mus musculus)
Samples (78)
GSM1527676 Homo sapiens Th1 Native H3
GSM1527677 Homo sapiens Th1 Native H3K4me3
GSM1527678 Homo sapiens Th2 Native H3
This SubSeries is part of SuperSeries:
GSE62486 T-bet recruits P-TEFb to super-enhancers to regulate T helper cell differentiation
Relations
BioProject PRJNA264228
SRA SRP049020

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE62482_RAW.tar 11.0 Mb (http)(custom) TAR (of BED, TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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