MicroRNA-125b is a key epigenetic regulatory factor that promotes nuclear transfer reprogramming
| Autor: | Jingcheng Zhang, Jun Liu, Chuan Zhou, Xin Liu, Mengyun Wang, Jianmin Su, Xiaonan Ma, Yongsheng Wang, Yong Zhang, Pengxiang Qu |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Nuclear Transfer Techniques Somatic cell cloning embryo Biology Methylation Biochemistry Epigenesis Genetic Histones Mice microRNA (miRNA) 03 medical and health sciences Histone H3 0302 clinical medicine Heterochromatin microRNA Histone methylation Animals Humans histone methylation Epigenetics Molecular Biology Transcription factor Hepatocyte Nuclear Factor 1-beta Base Sequence Lysine reprogramming Methyltransferases Cell Biology Molecular biology Repressor Proteins MicroRNAs HEK293 Cells 030104 developmental biology Gene Expression Regulation Somatic cell nuclear transfer Reprogramming 030217 neurology & neurosurgery Developmental Biology |
| Zdroj: | The Journal of Biological Chemistry |
| ISSN: | 0021-9258 |
| Popis: | Somatic cell nuclear transfer (SCNT)-mediated reprogramming is a rapid, efficient, and sophisticated process that reprograms differentiated somatic cells to a pluripotent state. However, many factors in this elaborate reprogramming process remain largely unknown. Here, we report that the microRNA (miR) miR-125b is an important component of SCNT-mediated reprogramming. Luciferase reporter assay, quantitative PCR, and Western blotting demonstrated that miR-125b directly binds the 3′-untranslated region of SUV39H1, encoding the histone-lysine N-methyltransferase SUV39H1, to down-regulate histone H3 lysine-9 tri-methylation (H3K9me3) in SCNT embryos. Furthermore, the miR-125b/SUV39H1 interaction induced loss of SUV39H1-mediated H3K9me3, caused heterochromatin relaxation, and promoted the development of SCNT embryos. Transcriptome analyses of SCNT blastomeres indicated that HNF1 homeobox B (HNF1B), a gene encoding a transcription factor downstream of and controlled by the miR-125b/SUV39H1 axis, is important for conferring developmental competence on preimplantation embryos. We conclude that miR-125b promotes SCNT-mediated nuclear reprogramming by targeting SUV39H1 to decrease the deposition of repressive H3K9me3 modifications. |
| Databáze: | OpenAIRE |
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