Widespread collaboration of Isw2 and Sin3-Rpd3 chromatin remodeling complexes in transcriptional repression
Widespread collaboration of Isw2 and Sin3-Rpd3 chromatin remodeling complexes in transcriptional repression
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DOI：
10.1128/mcb.21.19.6450-6460.2001
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发表时间：
2001-10-01
影响因子：
5.3
通讯作者：
Tsukiyama, T
中科院分区：
文献类型：
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作者：
Fazzio, TG;Kooperberg, C;Tsukiyama, T
酵母Isw 2染色质重塑复合物与Sin 3-Rpd 3组蛋白脱乙酰酶复合物平行发挥功能，以在Ume 6p募集后抑制早期减数分裂基因。对于这些基因中的许多基因，isw 2突变的影响被功能性Sin 3-Rpd 3复合物部分掩盖。为了鉴定被这些因素抑制或激活的基因的全部范围，并揭示Isw 2依赖性调节的隐藏靶点，我们使用cDNA微阵列进行了全基因组表达分析。我们发现Isw 2复合物的功能主要是在转录的抑制在一个平行的途径与Sin 3-Rpd 3复合物。除了Ume 6靶基因，我们发现，许多Ume 6-独立的基因在突变体中缺乏功能Isw 2和Sin 3-Rpd 3复合物去阻遏。相反，我们发现，ume 6突变体，但不是isw 2 sin 3或isw 2 rpd 3双突变体，有丝分裂染色体分离的保真度降低，这表明一个或多个功能的ume 6p是独立的sin 3-Rpd 3和Isw 2复合物。两个非减数分裂基因的染色质结构分析揭示了增加的DNase I的敏感性在其调控区域内的isw 2突变体，如前所述的一个减数分裂位点。这些数据表明，Isw 2复合物的功能在Ume 6依赖性和非依赖性基因座，以创建DNA酶I不可访问的染色质结构，通过调节定位或放置的核小体。
The yeast Isw2 chromatin remodeling complex functions in parallel with the Sin3-Rpd3 histone deacetylase complex to repress early meiotic genes upon recruitment by Ume6p. For many of these genes, the effect of an isw2 mutation is partially masked by a functional Sin3-Rpd3 complex. To identify the full range of genes repressed or activated by these factors and uncover hidden targets of Isw2-dependent regulation, we performed full genome expression analyses using cDNA microarrays. We find that the Isw2 complex functions mainly in repression of transcription in a parallel pathway with the Sin3-Rpd3 complex. In addition to Ume6 target genes, we find that many Ume6-independent genes are derepressed in mutants lacking functional Isw2 and Sin3-Rpd3 complexes. Conversely, we find that ume6 mutants, but not isw2 sin3 or isw2 rpd3 double mutants, have reduced fidelity of mitotic chromosome segregation, suggesting that one or more functions of Ume6p are independent of Sin3-Rpd3 and Isw2 complexes. Chromatin structure analyses of two nonmeiotic genes reveals increased DNase I sensitivity within their regulatory regions in an isw2 mutant, as seen previously for one meiotic locus. These data suggest that the Isw2 complex functions at Ume6-dependent and -independent loci to create DNase I-inaccessible chromatin structure by regulating the positioning or placement of nucleosomes.