The Krüppel-associated box repressor domain induces reversible and irreversible regulation of endogenous mouse genes by mediating different chromatin states
| Autor: | Xingyu Yang, Yue Ying, Ruilin Sun, Jian Fei, Jifang Mao, Zhugang Wang, Ying Kuang, Kai Zhao |
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| Rok vydání: | 2015 |
| Předmět: |
Chromatin Immunoprecipitation
Hypoxanthine Phosphoribosyltransferase Repressor Mice Transgenic Biology Real-Time Polymerase Chain Reaction Epigenesis Genetic Mice Genetics Animals Gene Cells Cultured DNA Primers Regulation of gene expression Early embryonic stage Base Sequence Gene regulation Chromatin and Epigenetics Nuclear Proteins DNA Methylation Chromatin Repressor Proteins Histone Gene Expression Regulation DNA methylation biology.protein Carrier Proteins Chromatin immunoprecipitation |
| Zdroj: | Nucleic Acids Research |
| ISSN: | 1362-4962 |
| Popis: | The Kruppel-associated box (KRAB) domain is a transcription repression module from the largest family of transcriptional regulators encoded by higher vertebrates. We developed a drug-controllable regulation system based on an artificial KRAB-containing repressor (tTS) that targets the endogenous Hprt gene to explore the regulatory mechanism and molecular basis of KRAB-containing regulators within the context of an endogenous gene in vivo. We show that KRAB can mediate irreversible and reversible regulation of endogenous genes in mouse that is dependent on embryonic developmental stage. KRAB-induced stable DNA methylation within the KRAB binding region during the early embryonic stage, resulting in irreversible gene repression. In later stages, KRAB mainly induced de-acetylation and methylation of histone, resulting in reversible gene repression. Thus, we have characterized the KRAB-mediated regulation system within the context of an endogenous gene and multiple spatiotemporal ranges, thereby providing a basis for identifying the function of KRAB-containing regulators and aiding development of novel KRAB-based gene regulation tools in vivo. |
| Databáze: | OpenAIRE |
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