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

	KDM1B is a histone H3K4 demethylase required to establish maternal genomic imprints
	Ciccone, DN; Su, H; Hevi, S; Gay, F; Lei, H; Bajko, J; Xu, GL; Li, E; Chen, TP
刊名	NATURE
	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
内容类型	期刊论文
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
推荐引用方式 GB/T 7714	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.