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OBF1 and Oct factors control the germinal center transcriptional program
- Source :
- Blood. 137(21)
- Publication Year :
- 2020
-
Abstract
- OBF1 is a specific coactivator of the POU family transcription factors OCT1 and OCT2. OBF1 and OCT2 are B cell–specific and indispensable for germinal center (GC) formation, but their mechanism of action is unclear. Here, we show by chromatin immunoprecipitation-sequencing that OBF1 extensively colocalizes with OCT1 and OCT2. We found that these factors also often colocalize with transcription factors of the ETS family. Furthermore, we showed that OBF1, OCT2, and OCT1 bind widely to the promoters or enhancers of genes involved in GC formation in mouse and human GC B cells. Short hairpin RNA knockdown experiments demonstrated that OCT1, OCT2, and OBF1 regulate each other and are essential for proliferation of GC-derived lymphoma cell lines. OBF1 downregulation disrupts the GC transcriptional program: genes involved in GC maintenance, such as BCL6, are downregulated, whereas genes related to exit from the GC program, such as IRF4, are upregulated. Ectopic expression of BCL6 does not restore the proliferation of GC-derived lymphoma cells depleted of OBF1 unless IRF4 is also depleted, indicating that OBF1 controls an essential regulatory node in GC differentiation.
- Subjects :
- 0301 basic medicine
Lipopolysaccharides
Chromatin Immunoprecipitation
Transcription, Genetic
Immunology
Mice, Transgenic
Biology
Biochemistry
Proto-Oncogene Protein c-ets-1
03 medical and health sciences
Mice
0302 clinical medicine
Cell Line, Tumor
Coactivator
Animals
Humans
RNA, Small Interfering
Enhancer
Transcription factor
B-Lymphocytes
POU domain
Lymphoma, Non-Hodgkin
Germinal center
Promoter
Cell Biology
Hematology
BCL6
Germinal Center
Recombinant Proteins
Cell biology
Chromatin
Mice, Inbred C57BL
030104 developmental biology
Gene Ontology
HEK293 Cells
030220 oncology & carcinogenesis
Trans-Activators
RNA Interference
Octamer Transcription Factor-2
Octamer Transcription Factor-1
Subjects
Details
- ISSN :
- 15280020
- Volume :
- 137
- Issue :
- 21
- Database :
- OpenAIRE
- Journal :
- Blood
- Accession number :
- edsair.doi.dedup.....97a1f6082492ef82cda45a282a68764f