气候变化领域集成服务门户(CCPortal): An in vivo screen of noncoding loci reveals that Daedalus is a gatekeeper of an Ikaros-dependent checkpoint during haematopoiesis

CCPortal

DOI	10.1073/PNAS.1918062118
	An in vivo screen of noncoding loci reveals that Daedalus is a gatekeeper of an Ikaros-dependent checkpoint during haematopoiesis
	Harman C.C.D.; Bailis W.; Zhao J.; Hill L.; Qu R.; Jackson R.P.; Shyer J.A.; Steach H.R.; Kluger Y.; Goff L.A.; Rinn J.L.; Williams A.; Henao-Mejia J.; Flavell R.A.
发表日期	2021
ISSN	00278424
卷号	118 期号:3
英文摘要	Haematopoiesis relies on tightly controlled gene expression patterns as development proceeds through a series of progenitors. While the regulation of hematopoietic development has been well studied, the role of noncoding elements in this critical process is a developing field. In particular, the discovery of new regulators of lymphopoiesis could have important implications for our understanding of the adaptive immune system and disease. Here we elucidate how a noncoding element is capable of regulating a broadly expressed transcription factor, Ikaros, in a lymphoid lineage-specific manner, such that it imbues Ikaros with the ability to specify the lymphoid lineage over alternate fates. Deletion of the Daedalus locus, which is proximal to Ikaros, led to a severe reduction in early lymphoid progenitors, exerting control over the earliest fate decisions during lymphoid lineage commitment. Daedalus locus deletion led to alterations in Ikaros isoform expression and a significant reduction in Ikaros protein. The Daedalus locus may function through direct DNA interaction as Hi-C analysis demonstrated an interaction between the two loci. Finally, we identify an Ikaros-regulated erythroid-lymphoid checkpoint that is governed by Daedalus in a lymphoid-lineage-specific manner. Daedalus appears to act as a gatekeeper of Ikaros's broad lineage-specifying functions, selectively stabilizing Ikaros activity in the lymphoid lineage and permitting diversion to the erythroid fate in its absence. These findings represent a key illustration of how a transcription factor with broad lineage expression must work in concert with noncoding elements to orchestrate hematopoietic lineage commitment. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Hematopoiesis; Ikaros; Lymphocytes; Noncoding
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/181011
作者单位	Department of Genetics, Yale School of Medicine, New Haven, CT 06520, United States; Howard Hughes Medical Institute, New Haven, CT 06520, United States; Division of Protective Immunity, Children's Hospital of Philadelphia, Philadelphia, PA 19104, United States; Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States; Department of Immunobiology, Yale School of Medicine, New Haven, CT 06520, United States; Department of Pathology, Yale School of Medicine, New Haven, CT 06510, United States; Program of Computational Biology and Bioinformatics, Yale University, New Haven, CT 06520, United States; Research Institute of Molecular Pathology, Vienna Biocenter, Vienna, 1030, Austria; Applied Mathematics Program, Yale University, New Haven, CT 06511, United States; Broad Institute of MIT and Harvard, Cambridge, MA 02142, United States; Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205,...
推荐引用方式 GB/T 7714	Harman C.C.D.,Bailis W.,Zhao J.,et al. An in vivo screen of noncoding loci reveals that Daedalus is a gatekeeper of an Ikaros-dependent checkpoint during haematopoiesis[J],2021,118(3).
APA	Harman C.C.D..,Bailis W..,Zhao J..,Hill L..,Qu R..,...&Flavell R.A..(2021).An in vivo screen of noncoding loci reveals that Daedalus is a gatekeeper of an Ikaros-dependent checkpoint during haematopoiesis.Proceedings of the National Academy of Sciences of the United States of America,118(3).
MLA	Harman C.C.D.,et al."An in vivo screen of noncoding loci reveals that Daedalus is a gatekeeper of an Ikaros-dependent checkpoint during haematopoiesis".Proceedings of the National Academy of Sciences of the United States of America 118.3(2021).