The product of the SNF2/SWI2 paralogue INO80 of Saccharomyces cerevisiae required for efficient expression of various yeast structural genes is part of a high-molecular-weight protein complex

The product of the SNF2/SWI2 paralogue INO80 of Saccharomyces cerevisiae required for efficient expression of various yeast structural genes is part of a high-molecular-weight protein complex
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DOI:
10.1046/j.1365-2958.1999.01390.x
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发表时间:
1999-05-01
影响因子:
3.6
通讯作者:
Schüller, HJ
Schüller, HJ
中科院分区:
生物学2区
文献类型:
--
作者:
Ebbert, R;Birkmann, A;Schüller, HJ

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酿酒酵母中磷脂生物合成的结构基因由Ino2p/Ino4p转录因子激活,该转录因子与ICRE启动子基序结合,并在没有肌醇的情况下调节基因的最大表达。我们发现INO80突变导致肌醇缺乏症是由于ICRE依赖的基因激活缺陷所致。相应的野生型基因INO80(=YGL150C)的产物与DNA依赖的ATPase Snf2p家族有很大的相似性,但SNF2基因剂量的增加并没有抑制INO80突变的表型,与Snf2p的NTP结合位点对应的Ino80p赖氨酸残基突变导致了一个无功能的蛋白,在INO80缺失突变中,ICRE介导的基因激活降低到野生型的16%,PHO5、GAL1、Cyc1和ICL1的最大表达也显著降低,因此,Ino80p影响了几个无关的转录因子,如凝胶过滤、凝胶过滤、凝胶过滤等Ino80p是一个超过1个丙二醛的高分子量复合体的一部分。与已发现的Snf2p类似,含有Ino80p的复合体可能通过作为可能作用于染色质的ATPase来影响几个无关结构基因的转录水平。
Structural genes of phospholipid biosynthesis in the yeast Saccharomyces cerevisiae are activated by the Ino2p/Ino4p transcription factor that binds to ICRE promoter motifs and mediates maximal gene expression in the absence of inositol. We identified the ino80 mutation causing inositol auxotrophy as a result of a defect in ICRE-dependent gene activation. The product of the corresponding wild-type gene INO80 (= YGL150C) shows significant similarity to the Snf2p family of DNA-dependent ATPases, Nevertheless, SNF2 in increased gene dosage did not suppress ino80 mutant phenotypes, Mutation of the Ino80p lysine residue corresponding to the NTP binding site of Snf2p led to a non-functional protein, In ino80 null mutants, gene activation mediated by an ICRE decreased to 16% of the wild-type level, Maximal expression of PHO5, GAL1, CYC1 and ICL1 was also significantly reduced, Thus, Ino80p affects several transcription factors involved in unrelated pathways, As demonstrated by gel filtration, Ino80p is part of a high-molecular-weight complex of more than 1 MDa. Similar to what was found for Snf2p, the Ino80p-containing complex may influence the transcriptional level of several unrelated structural genes by functioning as an ATPase that possibly acts on chromatin.