Genome-wide analysis of YY2 versus YY1 target genes.

Genome-wide analysis of YY2 versus YY1 target genes.
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DOI:
10.1093/nar/gkq112
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发表时间:
2010-07
影响因子:
14.9
通讯作者:
Schmidt EV
Schmidt EV
中科院分区:
生物学2区
文献类型:
--
作者:
Chen L;Shioda T;Coser KR;Lynch MC;Yang C;Schmidt EV

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阴阳1号(YY1)是一个控制细胞增殖、发育和DNA损伤反应的关键转录因子。逆转位在多个物种中独立地产生了额外的YY家族成员。尽管果蝇YY1[多同源(Pho)]及其同系物[多同源(Pho)]冗余地控制同源基因的表达,但YY1-同系物在其他物种中的调控作用尚未被研究过。事实上,哺乳动物YY1同源基因YY2的靶标是完全未知的。利用基因集浓缩分析,我们发现含有针对人YY1(ShYY1)及其同源物YY2(ShYY2)的短发夹环抑制RNA的慢病毒构建体引起了人类细胞中共享和可区分的基因集的显著变化。核糖体蛋白基因是shYY1和shYY2上调的最显著的基因组,尽管shYY1/2的联合敲除不是相加的。相反,shYY2逆转了shYY1的抗增殖作用,shYY2特别改变了紫外线损伤反应、血小板特异性基因和线粒体功能基因。我们发现,YY1或YY2的减少导致紫外线敏感度的反向变化,并且它们的组合损失逆转了它们各自的单独影响。我们的研究表明,人类YY2对YY1并不是多余的,而YY2是先前被认为是唯一对YY1做出反应的基因的重要调节因子。
Yin Yang 1 (YY1) is a critical transcription factor controlling cell proliferation, development and DNA damage responses. Retrotranspositions have independently generated additional YY family members in multiple species. Although Drosophila YY1 [pleiohomeotic (Pho)] and its homolog [pleiohomeotic-like (Phol)] redundantly control homeotic gene expression, the regulatory contributions of YY1-homologs have not yet been examined in other species. Indeed, targets for the mammalian YY1 homolog YY2 are completely unknown. Using gene set enrichment analysis, we found that lentiviral constructs containing short hairpin loop inhibitory RNAs for human YY1 (shYY1) and its homolog YY2 (shYY2) caused significant changes in both shared and distinguishable gene sets in human cells. Ribosomal protein genes were the most significant gene set upregulated by both shYY1 and shYY2, although combined shYY1/2 knock downs were not additive. In contrast, shYY2 reversed the anti-proliferative effects of shYY1, and shYY2 particularly altered UV damage response, platelet-specific and mitochondrial function genes. We found that decreases in YY1 or YY2 caused inverse changes in UV sensitivity, and that their combined loss reversed their respective individual effects. Our studies show that human YY2 is not redundant to YY1, and YY2 is a significant regulator of genes previously identified as uniquely responding to YY1.
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