Acetylation of GATA-1 is required for chromatin occupancy
Acetylation of GATA-1 is required for chromatin occupancy
复制标题
DOI：
10.1182/blood-2006-07-032847
复制
发表时间：
2006-12-01
期刊：
影响因子：
20.3
通讯作者：
Blobel, Gerd A.
中科院分区：
文献类型：
--
作者：
Lamonica, Janine M.;Vakoc, Christopher R.;Blobel, Gerd A.
所有3种造血加塔转录因子，加塔-1、加塔-2和加塔-3，都是乙酰化的，尽管这种修饰的体内作用尚不清楚。我们研究了加塔-1的乙酰化缺陷突变体在成熟红系细胞中的功能。我们发现，去除加塔-1中的乙酰化位点不会损害其核定位、稳态蛋白水平或其在体外结合裸加塔元件的能力。然而，染色质免疫沉淀（Chip）实验揭示突变体加塔-1在体内与所有检查的细胞靶位点的结合显著受损，包括通常被加塔-1激活和抑制的基因。总之，这些结果表明乙酰化调节加塔-1的染色质占据。这些发现指出了转录因子乙酰化的一个新功能，可能是通过促进与染色质模板在体内稳定结合所需的蛋白质相互作用。
All 3 hematopoietic GATA transcription factors, GATA-1, GATA-2, and GATA-3, are acetylated, although the in vivo role of this modification remains unclear. We examined the functions of an acetylation-defective mutant of GATA-1 in maturing erythroid cells. We found that removal of the acetylation sites in GATA-1 does not impair its nuclear localization, steady-state protein levels, or its ability to bind naked GATA elements in vitro. However, chromatin immunoprecipitation (Chip) experiments revealed that mutant GATA-1 was dramatically impaired in binding to all examined cellular target sites in vivo, including genes that are normally activated and repressed by GATA-1. Together, these results suggest that acetylation regulates chromatin occupancy of GATA-1. These findings point to a novel function for transcription factor acetylation, perhaps by facilitating protein interactions required for stable association with chromatin templates in vivo.