MafG sumoylation is required for active transcriptional repression
MafG sumoylation is required for active transcriptional repression
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DOI：
10.1128/mcb.02193-05
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发表时间：
2006-06-01
影响因子：
5.3
通讯作者：
Yamamoto, Masayuki
中科院分区：
文献类型：
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作者：
Motohashi, Hozumi;Katsuoka, Fumiki;Yamamoto, Masayuki
引发转录抑制的直接机制是简单地阻断激活因子的DNA结合位点。这种被动阻遏通常由缺乏内在阻遏物活性的转录因子介导。MafG是转录的双向调节因子，在其同源二聚体状态下是阻遏物，但当与p45异源二聚体化时是激活物。在这里，我们报告说，MafG是共轭SUMO-2/3在体内。为了阐明类小泛素化在调节MafG活性中可能的生理作用，我们评估了转基因小鼠和培养细胞中的突变型和野生型MafG。而类小泛素化缺陷的MafG激活p45依赖的转录正常，并不影响异二聚体的活性，抑制类小泛素化缺陷的MafG突变体在体内严重受损。MafG的SUMO依赖性阻遏活性对组蛋白去乙酰化酶的抑制敏感。因此，MafG的抑制不是通过竞争激活剂结合位点的简单被动抑制来实现的，而是需要sumoylation，然后通过招募含有组蛋白脱乙酰酶活性的抑制子复合物来介导转录抑制。
A straightforward mechanism for eliciting transcriptional repression would be to simply block the DNA binding site for activators. Such passive repression is often mediated by transcription factors that lack an intrinsic repressor activity. MafG is a bidirectional regulator of transcription, a repressor in its homodimeric state but an activator when heterodimerized with p45. Here, we report that MafG is conjugated to SUMO-2/3 in vivo. To clarify the possible physiological role(s) for sumoylation in regulating MafG activity, we evaluated mutant and wild-type MafG in transgenic mice and cultured cells. Whereas sumoylation-deficient MafG activated p45-dependent transcription normally and did not affect heterodimer activity, repression by the sumoylation-deficient MafG mutant was severely compromised in vivo. Furthermore, the SUMO-dependent repression activity of MafG was sensitive to histone deacetylase inhibition. Thus, repression by MafG is not achieved through simple passive repression by competing for the activator binding site but requires sumoylation, which then mediates transcriptional repression through recruitment of a repressor complex containing histone deacetylase activity.