核糖体RNA基因中TTF-I介导的启动子-终止子相互作用的表观遗传调控。
Epigenetic regulation of TTF-I-mediated promoter-terminator interactions of rRNA genes.
作者信息
Németh Attila, Guibert Sylvain, Tiwari Vijay Kumar, Ohlsson Rolf, Längst Gernot
机构信息
Department of Biochemistry III, University of Regensburg, Regensburg, Germany.
出版信息
EMBO J. 2008 Apr 23;27(8):1255-65. doi: 10.1038/emboj.2008.57. Epub 2008 Mar 20.
Abstract
Ribosomal RNA synthesis is the eukaryotic cell's main transcriptional activity, but little is known about the chromatin domain organization and epigenetics of actively transcribed rRNA genes. Here, we show epigenetic and spatial organization of mouse rRNA genes at the molecular level. TTF-I-binding sites subdivide the rRNA transcription unit into functional chromatin domains and sharply delimit transcription factor occupancy. H2A.Z-containing nucleosomes occupy the spacer promoter next to a newly characterized TTF-I-binding site. The spacer and the promoter proximal TTF-I-binding sites demarcate the enhancer. DNA from both the enhancer and the coding region is hypomethylated in actively transcribed repeats. 3C analysis revealed an interaction between promoter and terminator regions, which brings the beginning and end of active rRNA genes into close contact. Reporter assays show that TTF-I mediates this interaction, thereby linking topology and epigenetic regulation of the rRNA genes.
摘要
核糖体RNA合成是真核细胞的主要转录活动，但对于活跃转录的rRNA基因的染色质结构域组织和表观遗传学，人们了解甚少。在此，我们在分子水平上展示了小鼠rRNA基因的表观遗传学和空间组织。TTF-I结合位点将rRNA转录单元细分为功能性染色质结构域，并严格限定转录因子的占据情况。含有H2A.Z的核小体占据紧邻一个新鉴定的TTF-I结合位点的间隔区启动子。间隔区和启动子近端的TTF-I结合位点划定了增强子。在活跃转录的重复序列中，来自增强子和编码区的DNA均发生低甲基化。3C分析揭示了启动子和终止子区域之间的相互作用，这使活跃的rRNA基因的起始和末端紧密接触。报告基因检测表明，TTF-I介导了这种相互作用，从而将rRNA基因的拓扑结构与表观遗传调控联系起来。
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