Regulating the Regulators: The Role of Histone Deacetylase 1 (HDAC1) in Erythropoiesis.
Regulating the Regulators: The Role of Histone Deacetylase 1 (HDAC1) in Erythropoiesis.
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DOI：
10.3390/ijms21228460
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发表时间：
2020-11-11
影响因子：
5.6
通讯作者：
Qiu Y
中科院分区：
文献类型：
--
作者：
Kim MY;Yan B;Huang S;Qiu Y
组蛋白去乙酰化酶（HDAC）在真核细胞的转录调控中起重要作用。I类去乙酰化酶HDAC 1/2通常与阻遏物复合物结合，如Sin 3（开关独立3）、NuRD（核小体重塑和去乙酰化酶）和CoREST（RE 1沉默转录因子的辅阻遏物）复合物。已经显示HDAC 1与红细胞生成的所有必需转录因子相互作用并调节所有必需转录因子。在红细胞生成过程中，组蛋白脱乙酰酶活性显著降低。因此，HDAC活性的抑制促进红系分化。HDAC活性的降低不仅导致转录激活因子如加塔-1（GATA结合因子1）、TAL 1（TAL BHLH转录因子1）和KLF 1（Krüpple样因子1）的激活，而且还抑制转录抑制因子如PU. 1（推定致癌基因Spi-1）。组蛋白去乙酰化酶活性的降低主要是通过HDAC 1乙酰化，其减弱HDAC 1活性，并通过与HDAC 1的二聚化反式抑制HDAC 2活性。因此，HDAC 1的乙酰化可以将辅阻遏物复合物转化为用于基因激活的激活物复合物。HDAC 1还可以使在红细胞生成中起作用的非组蛋白脱乙酰化，因此通过HDAC 1增加了另一层基因调控。临床上，已经显示HDACi可以重新激活成人红系细胞中的胎儿珠蛋白。本文就HDAC 1在红细胞生成中的作用及其临床意义作一综述。
Histone deacetylases (HDACs) play important roles in transcriptional regulation in eukaryotic cells. Class I deacetylase HDAC1/2 often associates with repressor complexes, such as Sin3 (Switch Independent 3), NuRD (Nucleosome remodeling and deacetylase) and CoREST (Corepressor of RE1 silencing transcription factor) complexes. It has been shown that HDAC1 interacts with and modulates all essential transcription factors for erythropoiesis. During erythropoiesis, histone deacetylase activity is dramatically reduced. Consistently, inhibition of HDAC activity promotes erythroid differentiation. The reduction of HDAC activity not only results in the activation of transcription activators such as GATA-1 (GATA-binding factor 1), TAL1 (TAL BHLH Transcription Factor 1) and KLF1 (Krüpple-like factor 1), but also represses transcription repressors such as PU.1 (Putative oncogene Spi-1). The reduction of histone deacetylase activity is mainly through HDAC1 acetylation that attenuates HDAC1 activity and trans-repress HDAC2 activity through dimerization with HDAC1. Therefore, the acetylation of HDAC1 can convert the corepressor complex to an activator complex for gene activation. HDAC1 also can deacetylate non-histone proteins that play a role on erythropoiesis, therefore adds another layer of gene regulation through HDAC1. Clinically, it has been shown HDACi can reactivate fetal globin in adult erythroid cells. This review will cover the up to date research on the role of HDAC1 in modulating key transcription factors for erythropoiesis and its clinical relevance.
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影响因子：
5.3
作者：
Chen, XY;Bieker, JJ
通讯作者：
Bieker, JJ
影响因子：
8
作者：
Cantor, AB;Orkin, SH
通讯作者：
Orkin, SH
影响因子：
25
作者：
Dobbin MM;Madabhushi R;Pan L;Chen Y;Kim D;Gao J;Ahanonu B;Pao PC;Qiu Y;Zhao Y;Tsai LH
通讯作者：
Tsai LH
受遗传变异影响的 BCL11A 红系增强子决定胎儿血红蛋白水平。
DOI：
10.1126/science.1242088
发表时间：
2013-10-11
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Bauer DE;Kamran SC;Lessard S;Xu J;Fujiwara Y;Lin C;Shao Z;Canver MC;Smith EC;Pinello L;Sabo PJ;Vierstra J;Voit RA;Yuan GC;Porteus MH;Stamatoyannopoulos JA;Lettre G;Orkin SH
通讯作者：
Orkin SH
影响因子：
3.1
作者：
Amaravadi, L;Klemsz, MJ
通讯作者：
Klemsz, MJ