RUNX1 Regulates a Transcription Program That Affects the Dynamics of Cell Cycle Entry of Naive Resting B Cells.

Autor:	Thomsen I; Gene Regulation and Chromatin Group, MRC London Institute of Medical Sciences, London, United Kingdom., Kunowska N; Gene Regulation and Chromatin Group, MRC London Institute of Medical Sciences, London, United Kingdom., de Souza R; Gene Regulation and Chromatin Group, MRC London Institute of Medical Sciences, London, United Kingdom., Moody AM; Gene Regulation and Chromatin Group, MRC London Institute of Medical Sciences, London, United Kingdom., Crawford G; Department of Immunology and Inflammation, Imperial College London, London, United Kingdom., Wang YF; Bioinformatics and Computing, MRC London Institute of Medical Sciences, London, United Kingdom., Khadayate S; Bioinformatics and Computing, MRC London Institute of Medical Sciences, London, United Kingdom., Whilding C; Microscopy Facility, MRC London Institute of Medical Sciences, London, United Kingdom., Strid J; Department of Immunology and Inflammation, Imperial College London, London, United Kingdom., Karimi MM; Bioinformatics and Computing, MRC London Institute of Medical Sciences, London, United Kingdom.; Comprehensive Cancer Centre, School of Cancer & Pharmaceutical Sciences, King's College London, London, United Kingdom., Barr AR; Cell Cycle Control Group, MRC London Institute of Medical Sciences, London, United Kingdom; and.; Institute of Clinical Sciences, Imperial College London, London, United Kingdom., Dillon N; Gene Regulation and Chromatin Group, MRC London Institute of Medical Sciences, London, United Kingdom; niall.dillon@lms.mrc.ac.uk pierangela.sabbattini@imperial.ac.uk.; Institute of Clinical Sciences, Imperial College London, London, United Kingdom., Sabbattini P; Gene Regulation and Chromatin Group, MRC London Institute of Medical Sciences, London, United Kingdom; niall.dillon@lms.mrc.ac.uk pierangela.sabbattini@imperial.ac.uk.
Jazyk:	angličtina
Zdroj:	Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2021 Dec 15; Vol. 207 (12), pp. 2976-2991. Date of Electronic Publication: 2021 Nov 22.
DOI:	10.4049/jimmunol.2001367
Abstrakt:	RUNX1 is a transcription factor that plays key roles in hematopoietic development and in hematopoiesis and lymphopoiesis. In this article, we report that RUNX1 regulates a gene expression program in naive mouse B cells that affects the dynamics of cell cycle entry in response to stimulation of the BCR. Conditional knockout of Runx1 in mouse resting B cells resulted in accelerated entry into S-phase after BCR engagement. Our results indicate that Runx1 regulates the cyclin D2 ( Ccnd2 ) gene, the immediate early genes Fosl2 , Atf3 , and Egr2 , and the Notch pathway gene Rbpj in mouse B cells, reducing the rate at which transcription of these genes increases after BCR stimulation. RUNX1 interacts with the chromatin remodeler SNF-2-related CREB-binding protein activator protein (SRCAP), recruiting it to promoter and enhancer regions of the Ccnd2 gene. BCR-mediated activation triggers switching between binding of RUNX1 and its paralog RUNX3 and between SRCAP and the switch/SNF remodeling complex member BRG1. Binding of BRG1 is increased at the Ccnd2 and Rbpj promoters in the Runx1 knockout cells after BCR stimulation. We also find that RUNX1 exerts positive or negative effects on a number of genes that affect the activation response of mouse resting B cells. These include Cd22 and Bank1 , which act as negative regulators of the BCR, and the IFN receptor subunit gene Ifnar1 The hyperresponsiveness of the Runx1 knockout B cells to BCR stimulation and its role in regulating genes that are associated with immune regulation suggest that RUNX1 could be involved in regulating B cell tolerance. (Copyright © 2021 by The Authors.)
Databáze:	MEDLINE
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