期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2012
卷号：109
期号：46
页码：18845-18850
DOI：10.1073/pnas.1213951109
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Chromatin remodeling is essential for controlling the expression of genes during development. The histone-modifying enzyme G9a/KMT1C can act both as a coactivator and a corepressor of transcription. Here, we show that the dual function of G9a as a coactivator vs. a corepressor entails its association within two distinct protein complexes, one containing the coactivator Mediator and one containing the corepressor Jarid1a/KDM5A. Functionally, G9a is important in stabilizing the Mediator complex for gene activation, whereas its repressive function entails a coordinate action with the histone H3 lysine 4 (H3K4) demethylase Jarid1a for the maintenance of gene repression. The essential nature of cross-talk between the histone methyltransferase G9a and the demethylase Jarid1a is demonstrated on the embryonic Ey-globin gene, where the concurrent introduction of repressive histone marks (dimethylated H3K9 and dimethylated H3K27) and removal of activating histone mark (trimethylated H3K4) is required for maintenance of gene silencing. Taken together with our previous demonstration of cross-talk between UTX and MLL2 to mediate activation of the adult {beta}maj-globin gene, these data suggest a model where "active" and "repressive" cross-talk between histone-modifying enzymes coexist on the same multigene locus and play a crucial role in the precise control of developmentally regulated gene expression.
关键词：beta-globin locus ; epigenetics ; erythroid differentiation ; hemoglobin
