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首页> 外文期刊>Molecular and Cellular Biology >Mammary-Specific Gene Activation Is Defined by Progressive Recruitment of STAT5 during Pregnancy and the Establishment of H3K4me3 Marks
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Mammary-Specific Gene Activation Is Defined by Progressive Recruitment of STAT5 during Pregnancy and the Establishment of H3K4me3 Marks

机译：特定于乳腺的基因激活是由怀孕期间STAT5的逐步募集和H3K4me3标记的建立定义的

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Differentiation of mammary secretory epithelium during pregnancy is characterized by sequential activation of genes over several orders of magnitude. Although the transcription factor STAT5 is key to alveolar development, it is not clear to what extent it controls temporal activation of genetic programs in secretory epithelium. To uncover molecular mechanisms effecting progressive differentiation, we explored genome-wide STAT5 binding and H3K4me3 (i.e., trimethylated histone H3 at K4) marks in mammary tissues at early and midpregnancy and at parturition. STAT5 binding to genes induced during pregnancy was low in immature mammary tissue but increased with epithelial differentiation. Increased STAT5 binding was associated with the establishment of H3K4me3 marks and transcriptional activation. STAT5 binding preceded the formation of H3K4me3 marks in some mammary-specific genes. De novo STAT5 binding was also found at distal sites, indicating enhancers. Furthermore, we established an exhaustive mammary transcriptome. Through integration of RNA-seq and STAT5 and H3K4me4 ChIP-seq data, we discovered novel mammary-specific alternative promoters and genes, including noncoding RNAs. Our findings suggest that STAT5 is an early step in establishing transcription complexes on genes specifically expressed in mammary epithelium. This is the first study in an organ that links progressive chromatin occupancy of STAT5 to the acquisition of H3K4me3 marks and transcription during hormone-induced differentiation.
机译：怀孕期间乳腺分泌上皮的分化特征是基因在多个数量级上依次激活。尽管转录因子STAT5是肺泡发育的关键，但尚不清楚它在多大程度上控制了分泌上皮中遗传程序的暂时激活。为了揭示影响渐进分化的分子机制，我们探索了早孕，中孕和分娩时乳腺组织中全基因组STAT5结合和H3K4me3（即K4处的三甲基化组蛋白H3）标记。 STAT5与怀孕期间诱导的基因的结合在未成熟的乳腺组织中较低，但随着上皮分化而增加。 STAT5结合增加与H3K4me3标记的建立和转录激活有关。 STAT5结合在某些乳腺特异性基因中先于H3K4me3标记形成。在远端部位也发现了 De novo STAT5的结合，表明增强子。此外，我们建立了详尽的乳腺转录组。通过整合RNA-seq和STAT5和H3K4me4 ChIP-seq数据，我们发现了新型的乳腺特异性替代启动子和基因，包括非编码RNA。我们的发现表明，STAT5是在乳腺上皮中特异性表达的基因上建立转录复合物的早期步骤。这是在器官诱导的分化过程中，将STAT5的染色质的逐步积累与H3K4me3标记的获得和转录联系起来的器官中的第一项研究。

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