Transcriptional heterogeneity in the lactase gene within cell-type is linked to the epigenome.
Transcriptional heterogeneity in the lactase gene within cell-type is linked to the epigenome.
复制标题
细胞类型中乳糖酶基因的转录异质性与表观基因组有关。
DOI：
10.1038/srep41843
复制
发表时间：
2017-01-31
影响因子：
4.6
通讯作者：
Labrie V
中科院分区：
文献类型：
--
作者：
Oh E;Jeremian R;Oh G;Groot D;Susic M;Lee K;Foy K;Laird PW;Petronis A;Labrie V
组织学和遗传学上相同的细胞中的转录变异是组织中的普遍现象，然而赋予这种异质性的过程还没有很好地理解。为了确定影响因素，我们分析了与小鼠乳糖酶基因（Lct）的体内转录梯度相关的表观遗传特征，该基因发生在小肠近端至远端轴的肠上皮细胞中沿着。我们发现，增强子和启动子元件的表观遗传标记与肠上皮细胞中Lct的转录变异一致。年龄和表型特异性环境线索（断奶后乳糖暴露）诱导的表观遗传修饰和CTCF结合在选择的调控元件，这对应于肠道Lct mRNA梯度的改变的变化。因此，表观遗传修饰与CTCF在调控元件处的结合解释了相同类型细胞中Lct的转录梯度。肠上皮细胞内的表观遗传分化可能有助于肠亚区的功能特化。
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.