Imperial College London
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ProfessorJessicaStrid

Faculty of Medicine, Department of Immunology and Inflammation

Professor of Cellular Immunology
 
 
 
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Contact

 

+44 (0)20 3313 1475j.strid

 
 
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Location

 

9N15BCommonwealth BuildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Thomsen:2021:10.4049/jimmunol.2001367,
author = {Thomsen, I and Kunowska, N and de, Souza R and Moody, A-M and Crawford, G and Wang, Y-F and Khadayate, S and Whilding, C and Strid, J and Karimi, MM and Barr, AR and Dillon, N and Sabbattini, P},
doi = {10.4049/jimmunol.2001367},
journal = {Journal of Immunology},
pages = {2976--2991},
title = {RUNX1 regulates a transcription program that affects the dynamics of cell cycle entry of naive resting B cells},
url = {http://dx.doi.org/10.4049/jimmunol.2001367},
volume = {207},
year = {2021}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - 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.
AU  - Thomsen,I
AU  - Kunowska,N
AU  - de,Souza R
AU  - Moody,A-M
AU  - Crawford,G
AU  - Wang,Y-F
AU  - Khadayate,S
AU  - Whilding,C
AU  - Strid,J
AU  - Karimi,MM
AU  - Barr,AR
AU  - Dillon,N
AU  - Sabbattini,P
DO  - 10.4049/jimmunol.2001367
EP  - 2991
PY  - 2021///
SN  - 0022-1767
SP  - 2976
TI  - RUNX1 regulates a transcription program that affects the dynamics of cell cycle entry of naive resting B cells
T2  - Journal of Immunology
UR  - http://dx.doi.org/10.4049/jimmunol.2001367
UR  - https://www.ncbi.nlm.nih.gov/pubmed/34810221
UR  - http://hdl.handle.net/10044/1/93244
VL  - 207
ER  -
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