Identification of potential target genes of USP22 via ChIP-seq and RNA-seq analysis in HeLa cells.
Identification of potential target genes of USP22 via ChIP-seq and RNA-seq analysis in HeLa cells.
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通过 HeLa 细胞中的 ChIP-seq 和 RNA-seq 分析鉴定 USP22 的潜在靶基因
DOI：
10.1590/1678-4685-gmb-2017-0164
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发表时间：
2018
影响因子：
2.1
通讯作者：
Xiong J
中科院分区：
文献类型：
--
作者：
Gong Z;Liu J;Xie X;Xu X;Wu P;Li H;Wang Y;Li W;Xiong J
泛素特异性蛋白酶22（USP 22）是一种致癌基因，其表达在许多类型的癌症中上调。在细胞核中，USP 22作为佐贺的一个亚基来调节基因转录。然而，全基因组范围的USP 22结合位点及其直接靶基因尚不清楚。在这项研究中，我们在HeLa细胞中使用特异性抗体通过ChIP-seq表征了UPS 22和GCN 5的潜在基因组结合位点。有408个重叠的推定靶基因被USP 22和GCN 5结合。基序分析表明，USP 22和GCN 5结合的序列有两个共同的基序。基因本体（GO）和通路分析表明，USP 22和GCN 5靶向的基因参与不同的生理过程和通路。进一步的RNA-seq、GO和途径分析显示，UPS 22的敲低诱导了参与多种生理过程（如代谢过程）的许多基因的差异表达。ChIP-seq和RNA-seq数据的整合揭示了UPS 22结合到56个基因的启动子。这些发现可能为USP 22在宫颈癌发生过程中对基因表达的调控提供新的见解。
The ubiquitin-specific protease 22 (USP22) is an oncogene and its expression is upregulated in many types of cancer. In the nucleus, USP22 functions as one subunit of the SAGA to regulate gene transcription. However, the genome-wide USP22 binding sites and its direct target genes are yet clear. In this study, we characterized the potential genomic binding sites of UPS22 and GCN5 by ChIP-seq using specific antibodies in HeLa cells. There were 408 overlapping putative target genes bound by both USP22 and GCN5. Motif analysis showed that the sequences bound by USP22 and GCN5 shared two common motifs. Gene ontology (GO) and pathway analysis indicated that the genes targeted by USP22 and GCN5 were involved in different physiological processes and pathways. Further RNA-seq, GO and pathway analyses revealed that knockdown of UPS22 induced differential expression of many genes that participated in diverse physiological processes, such as metabolic process. Integration of ChIP-seq and RNA-seq data revealed that UPS22 bound to the promoters of 56 genes. These findings may provide new insights into the regulation of USP22 on gene expression during the development of cervical cancer.