Functional characterization of an amino-terminal region of HDAC4 that possesses MEF2 binding and transcriptional repressive activity
Functional characterization of an amino-terminal region of HDAC4 that possesses MEF2 binding and transcriptional repressive activity
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DOI：
10.1074/jbc.m301922200
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发表时间：
2003-06-27
影响因子：
4.8
通讯作者：
Wu, ZG
中科院分区：
文献类型：
--
作者：
Chan, JKL;Sun, LG;Wu, ZG
与全长组蛋白脱乙酰基酶（HDAC）4类似，其氨基末端（氨基酸1-208）没有羧基脱乙酰基酶结构域也已知有效地结合和抑制肌细胞增强因子2（MEF 2）。在这个抑制性氨基末端，我们进一步表明，一段90个氨基酸（119-208）显示MEF 2结合和抑制活性。同一区域也被发现与HDAC 1特异性相关，HDAC 1负责抑制作用。HDAC 4的氨基末端可以在体外与DNA结合的MEF 2结合，这表明HDAC 4不能简单地通过破坏MEF 2结合DNA的能力来抑制MEF 2。在体内，MEF 2诱导全长HDAC 4和HDAC 4-（1-208）两者的核转位，而核HDAC 4以及HDAC 4-（1-208）又特异性地将MEF 2隔离到不同的核体。此外，我们发现MyoD和HDAC 4在功能上相互拮抗以调节MEF 2活性。结合其他人的数据，我们的数据表明全长HDAC 4可以通过多个独立的抑制结构域抑制MEF 2。
Like the full-length histone deacetylase (HDAC) 4, its amino terminus (amino acids 1-208) without the carboxyl deacetylase domain is also known to effectively bind and repress myocyte enhancer factor 2 (MEF2). Within this repressive amino terminus, we further show that a stretch of 90 amino acids (119-208) displays MEF2 binding and repressive activity. The same region is also found to associate specifically with HDAC1 which is responsible for the repressive effect. The amino terminus of HDAC4 can associate with the DNA-bound MEF2 in vitro, suggesting that it does not repress MEF2 simply by disrupting the ability of MEF2 to bind DNA. In vivo, MEF2 induces nuclear translocation of both the full-length HDAC4 and HDAC4-(1-208), whereas the nuclear HDAC4 as well as HDAC4-(1-208) in turn specifically sequesters MEF2 to distinct nuclear bodies. In addition, we show that MyoD and HDAC4 functionally antagonize each other to regulate MEF2 activity. Combined with data from others, our data suggest that the full-length HDAC4 can repress MEF2 through multiple independent repressive domains.