气候变化领域集成服务门户(CCPortal): Runx1 and Runx3 drive progenitor to T-lineage transcriptome conversion in mouse T cell commitment via dynamic genomic site switching

CCPortal

DOI	10.1073/pnas.2019655118
	Runx1 and Runx3 drive progenitor to T-lineage transcriptome conversion in mouse T cell commitment via dynamic genomic site switching
	Shin B.; Hosokawa H.; Romero-Wolf M.; Zhou W.; Masuhara K.; Tobin V.R.; Levanon D.; Groner Y.; Rothenberg E.V.
发表日期	2021
ISSN	00278424
卷号	118 期号:4
英文摘要	Runt domain-related (Runx) transcription factors are essential for early T cell development in mice from uncommitted to committed stages. Single and double Runx knockouts via Cas9 show that target genes responding to Runx activity are not solely controlled by the dominant factor, Runx1. Instead, Runx1 and Runx3 are coexpressed in single cells; bind to highly overlapping genomic sites; and have redundant, collaborative functions regulating genes pivotal for T cell development. Despite stable combined expression levels across pro-T cell development, Runx1 and Runx3 preferentially activate and repress genes that change expression dynamically during lineage commitment, mostly activating T-lineage genes and repressing multipotent progenitor genes. Furthermore, most Runx target genes are sensitive to Runx perturbation only at one stage and often respond to Runx more for expression transitions than for maintenance. Contributing to this highly stage-dependent gene regulation function, Runx1 and Runx3 extensively shift their binding sites during commitment. Functionally distinct Runx occupancy sites associated with stage-specific activation or repression are also distinguished by different patterns of partner factor cobinding. Finally, Runx occupancies change coordinately at numerous clustered sites around positively or negatively regulated targets during commitment. This multisite binding behavior may contribute to a developmental “ratchet” mechanism making commitment irreversible. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	DNA binding site choice; Early T lymphocyte development; Functional genomics; Runx transcription factors; Transcriptional regulation
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180850
作者单位	Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, United States; Department of Immunology, Tokai University School of Medicine, Isehara, Kanagawa 259-1193, Japan; School of Veterinary Medicine, University of California, Davis, CA 95616, United States; Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, 76001, Israel
推荐引用方式 GB/T 7714	Shin B.,Hosokawa H.,Romero-Wolf M.,et al. Runx1 and Runx3 drive progenitor to T-lineage transcriptome conversion in mouse T cell commitment via dynamic genomic site switching[J],2021,118(4).
APA	Shin B..,Hosokawa H..,Romero-Wolf M..,Zhou W..,Masuhara K..,...&Rothenberg E.V..(2021).Runx1 and Runx3 drive progenitor to T-lineage transcriptome conversion in mouse T cell commitment via dynamic genomic site switching.Proceedings of the National Academy of Sciences of the United States of America,118(4).
MLA	Shin B.,et al."Runx1 and Runx3 drive progenitor to T-lineage transcriptome conversion in mouse T cell commitment via dynamic genomic site switching".Proceedings of the National Academy of Sciences of the United States of America 118.4(2021).