HISTONE ARGININE METHYLATION IN ES CELLS

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 在过去的十年中，有证据表明，很大一部分表观遗传信息是以组蛋白和相关DNA的化学修饰的形式传递的。我们的研究重点在于了解共价组蛋白修饰在脊椎动物发育和分化过程中调节基因表达模式的机制基础。我们正在描述组蛋白甲基化的下游效应器，或称“阅读器”，它识别甲基标记并将其转化为特定的生物结果。拟议的项目重点是识别识别组蛋白H3(H3R26me)上的精氨酸26的阅读器蛋白。这种修饰发生在赖氨酸27(H3K27)旁边，它是Polycomb介导组蛋白甲基化的关键残基。此外，我们最近已经证明，在胚胎干细胞的增强子元件上，相互排斥的H3K27ac和H3K27me3的修饰指定了它们的活跃状态和稳定状态。在这里，我们假设H3R26me可能与H3K27上的修改产生串扰，为了研究H3R26me的功能，我们建议识别和表征H3R26me阅读器。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. In the last decade evidence emerged that a substantial portion of epigenetic information is transmitted in a form of chemical modifications of histones and associated DNA. Our research focuses on understanding the mechanistic basis by which covalent histone modifications regulate gene expression patterns during vertebrate development and differentiation. We are characterizing downstream effectors of histone methylation, or "readers", which recognize the methyl marks and translate them into specific biological outcomes. The proposed project focuses on identifying reader proteins that recognize Arginine 26 on Histone H3 (H3R26me). This modification occurs right next to the lysine 27 (H3K27), which is a critical residue for Polycomb mediated histone methylation. Moreover, we had recently shown that mutually exclusive H3K27ac versus H3K27me3 modification at enhancer elements in embryonic stem cells specifies their active versus poised state. Here we hypothesize that H3R26me may cross talk with modifications at H3K27 and to investigate H3R26me function we propose to identify and characterize H3R26me readers.