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Series GSE29282 Query DataSets for GSE29282
Status Public on Aug 05, 2013
Title A Hybrid Mechanism of Action for BCL6 in B Cells Defined by Formation of Functionally Distinct Complexes at Enhancers and Promoters
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Summary BCL6 is crucial for B-cell activation and lymphomagenesis. We used integrative genomics to explore BCL6 mechanism in normal and malignant B-cells. Surprisingly, BCL6 assembled distinct complexes at enhancers vs. promoters. At enhancers BCL6 preferentially recruited SMRT, which mediated H3K27 deacetylation through HDAC3, antagonized p300 activity and repressed transcription, but without decommissioning enhancers. This provides a biochemical
basis for toggling enhancers from the active to poised state. Virtually all SMRT was bound with BCL6 suggesting that in B-cells BCL6 uniquely sequesters SMRT from other factors. In promoters BCL6 preferentially recruited BCOR, but most potently repressed promoters where it
formed a distinctive ternary complex with SMRT and BCOR. Promoter repression was associated with decreased H3K36me3, H3K79me2 and Pol II elongation, linking BCL6 to transcriptional pausing.
 
Overall design We identified the binding patterns of BCL6, SMRT, NCOR and BCOR corepressors in normal germinal center B cells and a DLBCL cell line (OCI-Ly1) using ChIP-seq. Additionally we treated lymphoma cells with siRNA against BCL6 and a non-targeted siRNA (NT control) and performed RNA-seq to identify the genes bound and repressed by BCL6. RNA-seq experiments were performed at 24h and 48h after siRNA treatments. Additional biological triplicate RNA-seq experiments were performed at 48h after BCL6 knockdown. Furthermore, a series of histone mark ChIP-seq and RNA polymerase ChIP-seq (total, Ser5-P and Ser2-P) were preformed to capture the chromatin states associated with the formation of BCL6 corepressor complexes.
 
Contributor(s) Hatzi K, Elemento O, Melnick A
Citation(s) 23911289
Submission date May 13, 2011
Last update date May 15, 2019
Contact name Katerina Hatzi
E-mail(s) kac2029@med.cornell.edu
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 (3)
GPL10999 Illumina Genome Analyzer IIx (Homo sapiens)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
GPL15433 Illumina HiSeq 1000 (Homo sapiens)
Samples (46)
GSM756309 OCI-LY1_Control_mRNAseq
GSM756310 OCI-LY1_siBCL6_24hrs_mRNAseq
GSM756311 OCI-LY1_siBCL6_48hrs_mRNAseq
Relations
BioProject PRJNA138597
SRA SRP007525

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

Supplementary file Size Download File type/resource
GSE29282_ChIP-seq_antibodies.txt.gz 400 b (ftp)(http) TXT
GSE29282_RAW.tar 13.2 Gb (http)(custom) TAR (of BED, BW, WIG)
SRA Run SelectorHelp
Processed data provided as supplementary file
Raw data are available in SRA

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