Subjects: Biology >> Biophysics >> Cell Biology submitted time 2016-05-11
Liu, Nan
Liu, Nan
Jiang, Yonghua
Meng, Lingjun
Xiong, Jun
Zhao, Zuodong
Zhou, Xiaohua
Li, Jia
Li, Hong
Zheng, Yong
Chen, She
Cai, Tao
Zhu, Bing
Liu, Nan
Zhu, Bing
Wu, Hui
Gao, Shaorong
Abstract： GLP and G9a are major H3K9 dimethylases and are essential for mouse early embryonic development. GLP and G9a both harbor ankyrin repeat domains that are capable of binding H3K9 methylation. However, the functional significance of their recognition of H3K9 methylation is unknown. Here, we report that the histone methyltransferase activities of GLP and G9a are stimulated by neighboring nucleosomes that are premethylated at H3K9. These stimulation events function in cis and are dependent on the H3K9 methylation binding activities of ankyrin repeat domains of GLP and G9a. Disruption of the H3K9 methylation-binding activity of GLP in mice causes growth retardation of embryos, ossification defects of calvaria, and postnatal lethality due to starvation of the pups. In mouse embryonic stem cells (ESCs) harboring a mutant GLP that lacks H3K9me1-binding activity, critical pluripotent genes, including Oct4 and Nanog, display inefficient establishment of H3K9me2 and delayed gene silencing during differentiation. Collectively, our study reveals a new activationmechanism for GLP and G9a that plays an important role in ESC differentiation and mouse viability.
Peer Review Status:
Awaiting Review
Subjects: Biology >> Biophysics submitted time 2016-05-05
Wang, Yixuan
Wang, Chenfei
Yang, Yuanyuan
Wang, Hong
Gao, Shaorong
Wu, Qian
Liu, Jing
Ding, Wenyu
Liu, Wensu
Bai, Ye
Wang, Xiaoqun
Yang, Peng
Abstract： Epigenetic regulatory complexes play key roles in the modulation of transcriptional regulation underlying neural stem cell (NSC) proliferation and progeny specification. How specific cofactors guide histone demethylase LSD1/KDM1A complex to regulate distinct NSC-related gene activation and repression in cortical neurogenesis remains unclear. Here we demonstrate that Rcor2, a co-repressor of LSD1, is mainly expressed in the central nervous system (CNS) and plays a key role in epigenetic regulation of cortical development. Depletion of Rcor2 results in reduced NPC proliferation, neuron population, neocortex thickness and brain size. We find that Rcor2 directly targets Dlx2 and Shh, and represses their expressions in developing neocortex. In addition, inhibition of Shh signals rescues the neurogenesis defects caused by Rcor2 depletion both in vivo and in vitro. Hence, our findings suggest that co-repressor Rcor2 is critical for cortical development by repressing Shh signalling pathway in dorsal telencephalon.
Peer Review Status:Awaiting Review
Hits
Hits
Downloads
Comment