Article

A model for mitotic inheritance of histone lysine methylation

Graduate Program, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China.
EMBO Reports (Impact Factor: 7.86). 11/2011; 13(1):60-7. DOI: 10.1038/embor.2011.206
Source: PubMed

ABSTRACT Histone lysine methylation has been implicated in epigenetic regulation of transcription. Using stable-isotope labelling and quantitative mass spectrometry, we analysed the dynamics of histone lysine methylation. Here we report that histone methylation levels are transiently reduced during S phase and are gradually re-established during subsequent cell cycle stages. However, despite the recovery of overall methylation levels before the next S phase, the methylation levels of parental and newly incorporated histones differ significantly. In addition, histone methylation levels are maintained at steady states by both restriction of methyltransferase activity and the active turnover of methyl groups in cells undergoing an extended G1/S phase arrest. Finally, we propose a 'buffer model' that unifies the imprecise inheritance of histone methylation and the faithful maintenance of underlying gene silencing.

0 Followers
 · 
129 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: The concept of epigenetics is now providing the mechanisms by which cells transfer their new environmental-change-induced phenotypes to their daughter cells. However, how extracellular or cytoplasmic environmental cues are connected to the nuclear epigenome remains incompletely understood. Recently emerging evidence suggests that epigenetic changes are correlated with metabolic changes via chromatin remodeling. As many human complex diseases including cancer harbor both epigenetic changes and metabolic dysregulation, understanding the molecular processes linking them has huge implications for disease pathogenesis and therapeutic intervention. In this review, the impacts of metabolic changes on cancer epigenetics are discussed, along with the current knowledge on cancer metabolism and epigenetics.
    Archives of Pharmacal Research 01/2015; DOI:10.1007/s12272-015-0561-3 · 1.75 Impact Factor
  • [Show abstract] [Hide abstract]
    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 activation mechanism for GLP and G9a that plays an important role in ESC differentiation and mouse viability. © 2015 Liu et al.; Published by Cold Spring Harbor Laboratory Press.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Recent studies have discovered phenotypes induced by a transient treatment or mutation that persist for multiple generations without mutations in DNA. Both invertebrates and vertebrates exhibit such inheritance, and a range of environmental factors can act as a trigger. Now referred to as Transgenerational Epigenetic Inheritance or TEI, this emerging field faces a big challenge-what molecular mechanisms account for inheritance of TEI phenotypes? This review describes examples of TEI and focuses on the possible role of histone methylation and small RNAs in mediating TEI. This article is part of a Special Issue entitled: Methylation Multifaceted Modification - looking at transcription and beyond, edited by Dr. Johnathan Whetstine.
    Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms 05/2014; 1839(12). DOI:10.1016/j.bbagrm.2014.05.011 · 5.44 Impact Factor

Full-text (2 Sources)

Download
7 Downloads
Available from
Jan 11, 2015