The Hematopoietic Stem and Progenitor Cell Cistrome: GATA Factor-Dependent cis-Regulatory Mechanisms.
The Hematopoietic Stem and Progenitor Cell Cistrome: GATA Factor-Dependent cis-Regulatory Mechanisms.
复制标题
DOI：
10.1016/bs.ctdb.2016.01.002
复制
发表时间：
2016
影响因子：
--
通讯作者：
Bresnick EH
中科院分区：
文献类型：
--
作者：
Hewitt KJ;Johnson KD;Gao X;Keles S;Bresnick EH
转录调节因子通过结合复杂的顺式调控元件来建立遗传网络，从而介导造血系统的发生和功能。虽然数千至数百万的任何给定的顺式元件存在于基因组中，但转录调节因子如何选择这些位点以及位点属性如何决定功能输出还没有很好地理解。解决该问题的指导性系统涉及控制重要发育和生理过程并与多种人类病理学相关的转录因子的加塔家族。虽然加塔因子结合含有序列加塔的DNA基序，但这些丰富的基序中只有非常小的子集被基因组占据。机制研究揭示了加塔因子调控的顺式元件的独特构型，其由一个E-box和一个下游的加塔基序组成，该基序被一个短的DNA间隔区隔开。在这些复合元件上的含有加塔-1或加塔-2的多蛋白复合物控制对哺乳动物胚胎中造血干细胞出现、造血祖细胞调节和红系细胞成熟至关重要的基因的转录。复合物的其他成分包括碱性螺旋-环-环转录因子Scl/TAL 1、其异二聚体伴侣E2 A和Lim结构域蛋白LMO 2和LDB 1。本文综述了E-box-加塔复合顺式元件的结构/功能，并有证据表明这些元件是造血干细胞和祖细胞顺式组遗传回路的关键组成部分。
Transcriptional regulators mediate the genesis and function of the hematopoietic system by binding complex ensembles of cis-regulatory elements to establish genetic networks. While thousands to millions of any given cis-element reside in a genome, how transcriptional regulators select these sites and how site attributes dictate the functional output is not well understood. An instructive system to address this problem involves the GATA family of transcription factors that control vital developmental and physiological processes and are linked to multiple human pathologies. Although GATA factors bind DNA motifs harboring the sequence GATA, only a very small subset of these abundant motifs are occupied in genomes. Mechanistic studies revealed a unique configuration of GATA factor-regulated cis-element consisting of an E-box and a downstream GATA motif separated by a short DNA spacer. GATA-1- or GATA-2-containing multi-protein complexes at these composite elements control transcription of genes critical for hematopoietic stem cell emergence in the mammalian embryo, hematopoietic progenitor cell regulation, and erythroid cell maturation. Other constituents of the complex include the basic helix-loop-loop transcription factor Scl/TAL1, its heterodimeric partner E2A, and the Lim domain proteins LMO2 and LDB1. This article reviews the structure/function of E-box-GATA composite cis-elements and evidence implicating these elements as critical constituents of a genetic circuit we term the hematopoietic stem and progenitor cell cistrome.
登录
查看更多内容
影响因子：
14.9
作者：
Bresnick EH;Katsumura KR;Lee HY;Johnson KD;Perkins AS
通讯作者：
Perkins AS
影响因子：
16
作者：
Crispino, JD;Lodish, MB;Orkin, SH
通讯作者：
Orkin, SH
DOI：
10.1073/pnas.212532399
发表时间：
2002-10-29
影响因子：
11.1
作者：
Chen, L;Segal, D;Westphal, H
通讯作者：
Westphal, H
影响因子：
46.9
作者：
Cho, Seung Woo;Kim, Sojung;Kim, Jin-Soo
通讯作者：
Kim, Jin-Soo
影响因子：
3.7
作者：
Bevilacqua, Ariana;Willis, Monte S.;Bultman, Scott J.
通讯作者：
Bultman, Scott J.