Histone acetyltransferase activity of p300 is required for transcriptional repression by the promyelocytic leukemia zinc finger protein
Histone acetyltransferase activity of p300 is required for transcriptional repression by the promyelocytic leukemia zinc finger protein
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DOI：
10.1128/mcb.25.13.5552-5566.2005
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发表时间：
2005-07-01
影响因子：
5.3
通讯作者：
Zelent, A
中科院分区：
文献类型：
--
作者：
Guidez, F;Howell, L;Zelent, A
组蛋白乙酰转移酶（RAT）活性的蛋白质，如p300，CBP和P/CAF在基因表达的激活中起重要作用。我们现在表明，HAT活性的p300也可以下调转录的DNA结合阻遏蛋白。早幼粒细胞白血病锌指（PLZF）最初被鉴定为在罕见的全反式维甲酸耐药急性早幼粒细胞白血病病例中与维甲酸受体α融合，是一种转录阻遏物，可将含组蛋白脱乙酰酶的辅阻遏物复合物募集到特异性DNA结合位点。PLZF在体内与p300结合，并且其抑制转录的能力特异性地依赖于p300的HAT活性和其C-末端C-2-H-2锌指基序中赖氨酸的乙酰化。PLZF的乙酰化位点突变体不抑制转录，并且在集落抑制测定中功能缺陷，尽管保留了其与辅阻遏物/组蛋白脱乙酰酶复合物相互作用的能力。这是由于PLZF的乙酰化激活了其在体外和体内结合特异性DNA序列的能力。两者合计，我们的研究结果表明，组蛋白去乙酰化酶依赖的转录抑制因子可以通过乙酰化正向调节，并指出一个意想不到的作用的共激活蛋白在转录抑制。
Histone acetyltransferase (RAT) activities of proteins such as p300, CBP, and P/CAF play important roles in activation of gene expression. We now show that the HAT activity of p300 can also be required for down-regulation of transcription by a DNA binding repressor protein. Promyelocytic leukemia zinc finger (PLZF), originally identified as a fusion with retinoic acid receptor alpha in rare cases of all-trans-retinoic acid-resistant acute promyelocytic leukemia, is a transcriptional repressor that recruits histone deacetylase-containing corepressor complexes to specific DNA binding sites. PLZF associates with p300 in vivo, and its ability to repress transcription is specifically dependent on HAT activity of p300 and acetylation of lysines in its C-terminal C-2-H-2 zinc finger motif. An acetylation site mutant of PLZF does not repress transcription and is functionally deficient in a colony suppression assay despite retaining its abilities to interact with corepressor/histone deacetylase complexes. This is due to the fact that acetylation of PLZF activates its ability to bind specific DNA sequences both in vitro and in vivo. Taken together, our results indicate that a histone deacetylase-dependent transcriptional repressor can be positively regulated through acetylation and point to an unexpected role of a coactivator protein in transcriptional repression.