Chd1 and yFACT act in opposition in regulating transcription
Chd1 and yFACT act in opposition in regulating transcription
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DOI：
10.1128/mcb.00978-07
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发表时间：
2007-09-01
影响因子：
5.3
通讯作者：
Stillman, David J.
中科院分区：
文献类型：
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作者：
Biswas, Debabrata;Dutta-Biswas, Rinku;Stillman, David J.
CHD 1编码具有两个染色质结构域的ATP依赖性染色质重塑物。CHD 1的缺失抑制由编码yFACT染色质重组复合物亚基的SPT 16或POB 3突变引起的温度敏感性生长缺陷。chd 1还抑制由spt 16突变与其他转录因子突变组合引起的合成缺陷，包括由spt 16突变与TATA结合蛋白（TBP）或TFIIA缺陷组合引起的合成致死性。在pob 3突变体中，TBP和RNA聚合酶11与GAL 1启动子的结合减少，导致GAL 1表达水平降低，并且通过去除Chd 1抑制所有三种缺陷。这些结果表明，Chd 1和yFACT在调节TBP结合启动子中具有相反的作用。此外，Chd 1的过表达在野生型细胞中是耐受的，但在spt 16突变体中是有毒的。此外，ATP酶和chromodomain都是Chd 1活性所必需的，与yFACT功能相反。与chd 1的抑制类似，SET 2组蛋白甲基转移酶的突变也抑制yFACT突变引起的缺陷。chd 1和set 2在抑制pob 3中是相加的，表明Chd 1和set 2在不同的通路中起作用。虽然人Chd 1已被证明结合H3-K4-Me，我们讨论的证据表明，酵母Chd 1既不结合H3-K4-Me，也不结合H3-K36-Me。
CHD1 encodes an ATP-dependent chromatin remodeler with two chromodomains. Deletion of CHD1 suppresses the temperature-sensitive growth defect caused by mutations in either SPT16 or POB3, which encode subunits of the yFACT chromatin-reorganizing complex. chd1 also suppresses synthetic defects caused by combining an spt16 mutation with other transcription factor mutations, including the synthetic lethality caused by combining an spt16 mutation with TATA binding protein (TBP) or TFIIA defects. Binding of TBP and RNA polymerase 11 to the GAL1 promoter is reduced in a pob3 mutant, resulting in low levels of GAL1 expression, and all three defects are suppressed by removing Chd1. These results suggest that Chd1 and yFACT have opposing roles in regulating TBP binding at promoters. Additionally, overexpression of Chd1 is tolerated in wild-type cells but is toxic in spt16 mutants. Further, both the ATPase and chromodomain are required for Chd1 activity in opposing yFACT function. Similar to the suppression by chd1, mutations in the SET2 histone methyltransferase also suppress defects caused by yFACT mutations. chd1 and set2 are additive in suppressing pob3, suggesting that Chd1 and Set2 act in distinct pathways. Although human Chd1 has been shown to bind to H3-K4-Me, we discuss evidence arguing that yeast Chd1 binds to neither H3-K4-Me nor H3-K36-Me.