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Series GSE59933 Query DataSets for GSE59933
Status Public on Mar 20, 2015
Title BCL6 orchestrates Tfh differentiation via multiple distinct mechanisms
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Tfh cells are required for T cell help to B cells, and BCL6 is the defining transcription factor of Tfh cells. However, the functions of Bcl6 in Tfh have largely remained unclear. Here we defined the BCL6 cistrome in primary human germinal center Tfh cells to assess mechanisms of BCL6 regulation of CD4 T cells, comparing and contrasting BCL6 function in T and B cells. BCL6 primarily acts as a repressor in Tfh cells, and BCL6 binding was associated with control of Tfh cell migration, TCR signaling, and repression of alternative cell fates. Interestingly, although some BCL6 bound genes possessed BCL6 DNA binding motifs, many BCL6-bound loci were instead characterized by the presence of DNA motifs for AP1 or STAT. AP1 complexes are key positive downstream mediators of TCR signaling and external stimuli. We show that BCL6 can directly bind AP1, and AP1 and BCL6 co-occupied BCL6 binding sites with AP1 motifs, suggesting that BCL6 subverts AP1 activity. These findings reveal that BCL6 has broad and multifaceted effects on Tfh biology, and provide insight into how this master regulator mediates distinct cell-context dependent phenotypes.
Overall design ChIP-seq experiments to identify the genome wide targets of BCL6 and the profiles of histone modifications H3K4me3, H3K4me1 and H3K27ac in CXCR5hi Tfh cells isolated from human tonsils.
Contributor(s) Hatzi K, Melnick A
Citation(s) 25824819
Submission date Jul 30, 2014
Last update date May 15, 2019
Contact name Katerina Hatzi
Organization name WCMC
Department Hematology/Oncology
Lab Ari Melnick
Street address 413 E 69th Street, BB-1462
City New York
State/province NY
ZIP/Postal code 10021
Country USA
Platforms (1)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
Samples (12)
GSM1462461 BCL6_REP1_ChIPSeq
GSM1462463 H3K4me1_REP1_ChIPSeq
BioProject PRJNA257089
SRA SRP045105

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

Supplementary file Size Download File type/resource
GSE59933_RAW.tar 5.1 Gb (http)(custom) TAR (of TXT, WIG)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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