RRC ID 31876
Author Kawakami E, Tokunaga A, Ozawa M, Sakamoto R, Yoshida N.
Title The histone demethylase Fbxl11/Kdm2a plays an essential role in embryonic development by repressing cell-cycle regulators.
Journal Mech Dev
Abstract Methylation and de-methylation of histone lysine residues play pivotal roles in mammalian early development; these modifications influence chromatin architecture and regulate gene transcription. Fbxl11 (F-box and leucine-rich repeat 11)/Kdm2a is a histone demethylase that selectively removes mono- and di-methylation from histone H3K36. Previously, two other histone H3K36 demethylases (Jmjd5 or Fbxl10) were analyzed based on the phenotypes of the corresponding knockout (KO) mice; the results of those studies implicated H3K36 demethylases in cell proliferation, apoptosis, and senescence (Fukuda et al., 2011; Ishimura et al., 2012). To elucidate the physiological role of Fbxl11, we generated and examined Fbxl11 KO mice. Fbxl11 was expressed throughout the body during embryogenesis, and the Fbxl11 KO mice exhibited embryonic lethality at E10.5-12.5, accompanied with severe growth defects leading to reduced body size. Furthermore, knockout of Fbxl11 decreased cell proliferation and increased apoptosis. The lack of Fbxl11 resulted in downregulation of the Polycomb group protein (PcG) Ezh2, PcG mediated H2A ubiquitination and upregulation of the cyclin-dependent kinase inhibitor p21Cip1. Taken together, our findings suggest that Fbxl11 plays an essential role in embryonic development and homeostasis by regulating cell proliferation and survival.
Volume 135
Pages 31-42
Published 2015-2-1
DOI 10.1016/j.mod.2014.10.001
PII S0925-4773(14)00067-7
PMID 25463925
MeSH Animals Cell Cycle Proteins / genetics Cell Cycle Proteins / metabolism* Cell Line Cell Proliferation Cell Survival Embryo, Mammalian / cytology Embryo, Mammalian / enzymology Embryonic Development Female Gene Expression Gene Expression Regulation, Developmental Genes, Lethal Histones / metabolism Jumonji Domain-Containing Histone Demethylases / physiology* Male Mice, Inbred C57BL Mice, Knockout Polycomb-Group Proteins / metabolism Protein Processing, Post-Translational
IF 2.126
Times Cited 29
Mice RBRC01834