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KDM1B is a histone H3K4 demethylase required to establish maternal genomic imprints

文献类型:期刊论文

作者Ciccone, DN; Su, H; Hevi, S; Gay, F; Lei, H; Bajko, J; Xu, GL; Li, E; Chen, TP
刊名NATURE
出版日期2009
卷号461期号:7262页码:415-U115
通讯作者Chen, TP (reprint author), Novartis Inst Biomed Res, Epigenet Program, 250 Massachusetts Ave, Cambridge, MA 02139 USA.,taiping.chen@novartis.com
英文摘要Differential DNA methylation of the paternal and maternal alleles regulates the parental origin-specific expression of imprinted genes in mammals(1,2). The methylation imprints are established in male and female germ cells during gametogenesis, and the de novo DNA methyltransferase DNMT3A and its cofactor DNMT3L are required in this process(3-5). However, the mechanisms underlying locus-and parental-specific targeting of the de novo DNA methylation machinery in germline imprinting are poorly understood. Here we show that amine oxidase (flavin-containing) domain 1 (AOF1), a protein related to the lysine demethylase KDM1 (also known as LSD1)(6), functions as a histone H3 lysine 4 (H3K4) demethylase and is required for de novo DNA methylation of some imprinted genes in oocytes. AOF1, now renamed lysine demethylase 1B (KDM1B) following a new nomenclature(7), is highly expressed in growing oocytes where genomic imprints are established. Targeted disruption of the gene encoding KDM1B had no effect on mouse development and oogenesis. However, oocytes from KDM1B-deficient females showed a substantial increase in H3K4 methylation and failed to set up the DNA methylation marks at four out of seven imprinted genes examined. Embryos derived from these oocytes showed biallelic expression or biallelic suppression of the affected genes and died before mid-gestation. Our results suggest that demethylation of H3K4 is critical for establishing the DNA methylation imprints during oogenesis.
学科主题Science & Technology - Other Topics
类目[WOS]Multidisciplinary Sciences
关键词[WOS]CONTROLS DNA METHYLATION ; CRYSTAL-STRUCTURE ; DNMT3L ; METHYLTRANSFERASE ; MAINTENANCE ; GENE ; LSD1
收录类别SCI
语种英语
WOS记录号WOS:000269828100044
版本出版稿
源URL[http://202.127.25.143/handle/331003/1304]  
专题上海生化细胞研究所_上海生科院生化细胞研究所
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Ciccone, DN,Su, H,Hevi, S,et al. KDM1B is a histone H3K4 demethylase required to establish maternal genomic imprints[J]. NATURE,2009,461(7262):415-U115.
APA Ciccone, DN.,Su, H.,Hevi, S.,Gay, F.,Lei, H.,...&Chen, TP.(2009).KDM1B is a histone H3K4 demethylase required to establish maternal genomic imprints.NATURE,461(7262),415-U115.
MLA Ciccone, DN,et al."KDM1B is a histone H3K4 demethylase required to establish maternal genomic imprints".NATURE 461.7262(2009):415-U115.

入库方式: OAI收割

来源:上海生物化学与细胞生物学研究所

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