Friend of GATA-1-independent transcriptional repression: a novel mode of GATA-1 function

Friend of GATA-1-independent transcriptional repression: a novel mode of GATA-1 function
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DOI:
10.1182/blood-2007-02-072983
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发表时间:
2007-06-15
期刊:
影响因子:
20.3
通讯作者:
Bresnick, Emery H.
Bresnick, Emery H.
中科院分区:
医学1区
文献类型:
--
作者:
Johnson, Kirby D.;Boyer, Meghan E.;Bresnick, Emery H.

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与加塔-1相互作用的蛋白质Friend Of加塔-1(FOG-1)对于许多加塔-1靶基因的适当转录激活和抑制是必需的。尽管已经描述了由加塔-1进行的非FOG-1依赖性激活,但是所有已知的加塔-1介导的抑制的实例都是FOG-1依赖性的。在加塔-1-null G1 E细胞系中,野生型加塔-1或加塔-1的FOG-1结合缺陷突变体的雌激素受体配体结合结构域(ER)嵌合体在β-雌二醇激活后类似地抑制了几个基因。在表达ER-GATA-1的FOG-1-null细胞系中和在离体红细胞生成期间也发生抑制。在Lyl 1和Rgs 18位点,我们发现加塔-1和加塔-2高度限制性占据,表明这些基因是加塔因子调控的直接靶标。对不依赖于FOG-1的被加塔-1抑制的基因的鉴定定义了加塔-1介导的转录调节的新模式。
The GATA-1 -interacting protein Friend Of GATA-1 (FOG-1) is essential for the proper transcriptional activation and repression of numerous GATA-1 target genes. Although FOG-1 -independent activation by GATA-1 has been described, all known examples of GATA-1-mediated repression are FOG-1 dependent. In the GATA-1-null G1E cell line, estrogen receptor ligand binding domain (ER) chimeras of either wild-type GATA-1 or a FOG-1-binding defective mutant of GATA-1 repressed several genes similarly upon activation with P-estradiol. Repression also occurred in a FOG-1-null cell line expressing ER-GATA-1 and during ex vivo erythropoiesis. At the Lyl1 and Rgs18 loci, we found highly restricted occupancy by GATA-1 and GATA-2, indicating that these genes are direct targets of GATA factor regulation. The identification of genes repressed by GATA-1 independent of FOG-1 defines a novel mode of GATA-1-mediated transcriptional regulation.