IRUS Total

RUNX1 regulates a transcription program that affects the dynamics of cell cycle entry of naive resting B cells

File Description SizeFormat 
Thomsen et al.pdfPublished version3.24 MBAdobe PDFView/Open
Title: RUNX1 regulates a transcription program that affects the dynamics of cell cycle entry of naive resting B cells
Authors: Thomsen, I
Kunowska, N
De Souza, R
Moody, A-M
Crawford, G
Wang, Y-F
Khadayate, S
Whilding, C
Strid, J
Karimi, MM
Barr, AR
Dillon, N
Sabbattini, P
Item Type: Journal Article
Abstract: 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.
Issue Date: 15-Dec-2021
Date of Acceptance: 28-Sep-2021
URI: http://hdl.handle.net/10044/1/93244
DOI: 10.4049/jimmunol.2001367
ISSN: 0022-1767
Publisher: American Association of Immunologists
Start Page: 2976
End Page: 2991
Journal / Book Title: Journal of Immunology
Volume: 207
Issue: 12
Copyright Statement: © 2021 by The Authors. This article is distributed under the terms of the CC BY 4.0 Unported license (https://creativecommons.org/licenses/by/4.0/)
Keywords: 1107 Immunology
Publication Status: Published
Conference Place: United States
Online Publication Date: 2021-12-06
Appears in Collections:Department of Immunology and Inflammation
Institute of Clinical Sciences
Faculty of Medicine

This item is licensed under a Creative Commons License Creative Commons