Histone deacetylase 3 binds to and regulates the multifunctional transcription factor TFII-I
Histone deacetylase 3 binds to and regulates the multifunctional transcription factor TFII-I
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DOI：
10.1074/jbc.m206528200
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发表时间：
2003-01-17
影响因子：
4.8
通讯作者：
Seto, E
中科院分区：
文献类型：
--
作者：
Wen, YD;Cress, WD;Seto, E
组蛋白脱乙酰基酶3（HDAC 3）是人类I类组蛋白脱乙酰基酶的四个成员之一，其通过核心组蛋白的氨基末端尾部中的乙酰基赖氨酸的脱乙酰化参与转录抑制。在使用抗HDAC 3的免疫亲和纯化中，转录因子TFII-I与HDAC 3共纯化。HDAC 3-TFII-I相互作用的特异性通过表位标记的蛋白质的共免疫沉淀、GST下拉测定和间接免疫荧光的蛋白质共定位来证实。抗TFII-I免疫沉淀物含有组蛋白脱乙酰酶酶活性。突变分析表明，HDAC 3的羧基端（残基373-401）和TFII-I的残基363-606是HDAC 3-TFII-I相互作用所必需的。TFII-I的转录激活被HDAC 3的过表达严重降低。这些结果表明，HDAC 3调节TFII-I的一些功能，并提供组蛋白脱乙酰酶和多功能转录激活因子之间的联系。
Histone deacetylase 3 (HDAC3) is one of four members of the human class I histone deacetylases that are implicated in transcriptional repression through deacetylation of acetyllysines in amino-terminal tails of core histones. In an immunoaffinity purification using anti-HDAC3, transcription factor TFII-I copurified with HDAC3. Specificity of the HDAC3-TFII-I interaction was confirmed by coimmunoprecipitation of epitope-tagged proteins, GST pull-down assays, and protein colocalization with indirect immunofluorescence. An anti-TFII-I immunoprecipitate contained histone deacetylase enzymatic activity. Mutational analyses revealed that the carboxyl-terminal of HDAC3 (residues 373-401) and residues 363-606 of TFII-I were required for the HDAC3-TFII-I interaction. Transcriptional activation by TFII-I was severely reduced by overexpression of HDAC3. These results suggest that HDAC3 modulates some of the functions of TFII-I and provides a link between histone deacetylase and a multifunctional transcriptional activator.