NDLI: OBF1 and Oct factors control the germinal center transcriptional program

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OBF1 and Oct factors control the germinal center transcriptional program

Content Provider	Scilit
Author	Song, Shuang Cao, Chun Choukrallah, Mohamed-Amin Tang, Fengyuan Christofori, Gerhard Kohler, Hubertus Wu, Fabian Fodor, Barna D. Frederiksen, Mathias Willis, Simon N. Jackson, Jacob T. Nutt, Stephen L. Dirnhofer, Stefan Stadler, Michael B. Matthias, Patrick
Copyright Year	2021
Description	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.
Related Links	https://ashpublications.org/blood/article-pdf/doi/10.1182/blood.2020010175/1798933/blood.2020010175.pdf
Ending Page	2934
Page Count	15
Starting Page	2920
DOI	10.1182/blood.2020010175
Journal	Blood
Issue Number	21
Volume Number	137
Language	English
Publisher	American Society of Hematology
Publisher Date	2021-05-27
Access Restriction	Open
Subject Keyword	Research and Experimental Medicine Transcription Factors Chromatin Oct1 Oct2 Transcriptional Program Obf1 Downregulated Colocalizes Irf4 Bcl6 Journal: Blood (Vol- 134, Issue- 21)
Content Type	Text
Resource Type	Article

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