Krembil Family Epigenetics Laboratory, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
Center for Epigenetics, Van Andel Research Institute, Grand Rapids, MI, USA.
Sci Rep. 2017 Jan 31;7:41843. doi: 10.1038/srep41843.
Transcriptional variation in histologically- and genetically- identical cells is a widespread phenomenon in tissues, yet the processes conferring this heterogeneity are not well understood. To identify contributing factors, we analyzed epigenetic profiles associated with the in vivo transcriptional gradient of the mouse lactase gene (Lct), which occurs in enterocytes along the proximal-to-distal axis of the small intestine. We found that epigenetic signatures at enhancer and promoter elements aligns with transcriptional variation of Lct in enterocytes. Age and phenotype-specific environmental cues (lactose exposure after weaning) induced changes to epigenetic modifications and CTCF binding at select regulatory elements, which corresponded to the alterations in the intestinal Lct mRNA gradient. Thus, epigenetic modifications in combination with CTCF binding at regulatory elements account for the transcriptional gradient in Lct in cells of the same type. Epigenetic divergence within enterocytes may contribute to the functional specialization of intestinal subregions.
组织中存在着一种广泛存在的现象，即组织学和遗传学上相同的细胞存在转录变异，但赋予这种异质性的过程尚不清楚。为了确定促成这种变异的因素，我们分析了与小鼠乳糖酶基因（Lct）体内转录梯度相关的表观遗传特征，该基因沿小肠近端-远端轴在肠细胞中表达。我们发现，增强子和启动子元件的表观遗传特征与肠细胞中 Lct 的转录变异相吻合。年龄和表型特异性环境线索（断奶后乳糖暴露）诱导了特定调控元件的表观遗传修饰和 CTCF 结合的变化，这与肠道 Lct mRNA 梯度的改变相对应。因此，表观遗传修饰与调控元件上的 CTCF 结合共同解释了相同类型细胞中 Lct 的转录梯度。肠细胞内的表观遗传差异可能导致肠道亚区的功能特化。
