OBF1 and Oct factors control the germinal center transcriptional program.

Autor:	Song S; Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.; Faculty of Sciences and., Cao C; Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland., Choukrallah MA; Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland., Tang F; Department of Biomedicine, University of Basel, Basel, Switzerland., Christofori G; Department of Biomedicine, University of Basel, Basel, Switzerland., Kohler H; Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland., Wu F; Novartis Institutes for Biomedical Research, Basel, Switzerland., Fodor BD; Novartis Institutes for Biomedical Research, Basel, Switzerland., Frederiksen M; Novartis Institutes for Biomedical Research, Basel, Switzerland., Willis SN; The Walter & Eliza Hall Institute of Medical Research, Parkville, VIC, Australia.; Department of Medical Biology, University of Melbourne, Parkville, VIC, Australia., Jackson JT; The Walter & Eliza Hall Institute of Medical Research, Parkville, VIC, Australia.; Department of Medical Biology, University of Melbourne, Parkville, VIC, Australia., Nutt SL; The Walter & Eliza Hall Institute of Medical Research, Parkville, VIC, Australia.; Department of Medical Biology, University of Melbourne, Parkville, VIC, Australia., Dirnhofer S; University Hospital Basel, Basel, Switzerland; and., Stadler MB; Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.; Faculty of Sciences and.; Swiss Institute of Bioinformatics, Basel, Switzerland., Matthias P; Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.; Faculty of Sciences and.
Jazyk:	angličtina
Zdroj:	Blood [Blood] 2021 May 27; Vol. 137 (21), pp. 2920-2934.
DOI:	10.1182/blood.2020010175
Abstrakt:	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. (© 2021 by The American Society of Hematology.)
Databáze:	MEDLINE
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