Transcriptional regulation by GATA1 and GATA2 during erythropoiesis
Transcriptional regulation by GATA1 and GATA2 during erythropoiesis
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DOI：
10.1007/s12185-011-0770-6
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发表时间：
2011-02
影响因子：
2.1
通讯作者：
Mikiko Suzuki;R. Shimizu;Masayuki Yamamoto
中科院分区：
文献类型：
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作者：
Mikiko Suzuki;R. Shimizu;Masayuki Yamamoto
转录因子GATA1调节红系细胞中的多个基因。然而，GATA1在红细胞生成过程中调节靶基因表达的方式仍有待阐明。GATA1对基因的调控有三种机制。首先，单个靶基因对细胞GATA1可能有多个离散的阈值。GATA1在红细胞生成过程中有一个动态的表达谱，因此一组GATA1靶基因的表达可能在细胞GATA1的特定分化阶段被触发。其次，GATA1靶基因的表达可能至少部分地被占据GATA结合基序的GATA2所修饰。GATA2在红细胞生成中比GATA1更早表达，GATA2与GATA2的结合可能使GATA1通过表观遗传重塑获得GATA基序，从而促进靶基因的表达。第三，针对每个靶基因的其他调控分子可能与GATA1协同发挥作用。如果这些辅因子的表达需要GATA1，就会形成一个调控网络，从而延迟相关基因的表达。我们认为，在体内，GATA1对红系基因的阶段特异性调控是通过这些机制的组合来严格控制的。
The transcription factor GATA1 regulates multiple genes in erythroid lineage cells. However, the means by which GATA1 regulates the expression of target genes during erythropoiesis remains to be elucidated. Three mechanisms have been postulated for the regulation of genes by GATA1. First, individual target genes may have multiple discrete thresholds for cellular GATA1. GATA1 has a dynamic expression profile during erythropoiesis, thus the expression of a set of GATA1 target genes may be triggered at a given stage of differentiation by cellular GATA1. Second, the expression of GATA1 target genes may be modified, at least in part, by GATA2 occupying the GATA-binding motifs. GATA2 is expressed earlier in erythropoiesis than GATA1, and prior GATA2 binding may afford GATA1 access to GATA motifs through epigenetic remodeling and thus facilitate target gene expression. Third, other regulatory molecules specific to each target gene may function cooperatively with GATA1. If GATA1 is required for the expression of such cofactors, a regulatory network will be formed and relevant gene expression will be delayed. We propose that the stage-specific regulation of erythroid genes by GATA1 is tightly controlled through a combination of these mechanisms in vivo.