University of Washington, Seattle, WA 98195, USA.
Mol Cell. 2010 Nov 24;40(4):594-605. doi: 10.1016/j.molcel.2010.10.028.
The stable and heritable H3K27-methyl mark suppresses transcription of lineage-specific genes in progenitor cells. During developmental transitions, histone demethylases are required to dramatically alter epigenetic and gene expression states to create new cell-specific profiles. It is unclear why demethylase proteins that antagonize polycomb-mediated repression continue to be expressed in terminally differentiated cells where further changes in H3K27 methylation could be deleterious. In this study, we show that the H3K27 demethylases, Jmjd3 and UTX, mediate a functional interaction between the lineage-defining T-box transcription factor family and a Brg1-containing SWI/SNF remodeling complex. Importantly, Jmjd3 is required for the coprecipitation of Brg1 with the T-box factor, T-bet, and this interaction is necessary for Ifng remodeling in differentiated Th1 cells. Thus, Jmjd3 has a required role in general chromatin remodeling that is independent from its H3K27 demethylase potential. This function for H3K27 demethylase proteins may explain their presence in differentiated cells where the epigenetic profile is already established.
稳定且可遗传的 H3K27-甲基化标记抑制祖细胞中谱系特异性基因的转录。在发育转变过程中，组蛋白去甲基酶需要显著改变表观遗传和基因表达状态，以创建新的细胞特异性特征。目前尚不清楚为什么拮抗多梳蛋白介导的抑制作用的去甲基酶蛋白在终末分化细胞中继续表达，因为 H3K27 甲基化的进一步变化可能是有害的。在这项研究中，我们表明 H3K27 去甲基酶 Jmjd3 和 UTX 介导了谱系定义性 T 盒转录因子家族与包含 Brg1 的 SWI/SNF 重塑复合物之间的功能相互作用。重要的是，Jmjd3 是 Brg1 与 T 盒因子 T-bet 共沉淀所必需的，这种相互作用对于分化的 Th1 细胞中 Ifng 的重塑是必需的。因此，Jmjd3 在一般染色质重塑中具有必需的作用，而与它的 H3K27 去甲基酶潜力无关。H3K27 去甲基酶蛋白的这种功能可能解释了它们在已建立表观遗传特征的分化细胞中的存在。
