From genes to milk: genomic organization and epigenetic regulation of the mammary transcriptome.
From genes to milk: genomic organization and epigenetic regulation of the mammary transcriptome.
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DOI：
10.1371/journal.pone.0075030
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Rijnkels M
中科院分区：
文献类型：
--
作者：
Lemay DG;Pollard KS;Martin WF;Freeman Zadrowski C;Hernandez J;Korf I;German JB;Rijnkels M
即使在缺乏操纵子的基因组中，基因在基因组中的位置也会影响其表达的潜力。邻近基因共表达的机制尚不完全清楚。以哺乳和乳腺为模型系统，探讨染色质状态参与基因邻域协同调控的假说。乳腺代表了一种独特的进化模式，由于其最近出现，在脊椎动物基因组的背景下。了解乳腺是如何被调节来产生乳汁的，对人类哺乳和乳业也具有生物医学和农业上的重要性。在这里，我们整合表观基因组学和转录组学数据来开发一个全面的调控模型。利用妊娠和哺乳期小鼠的表达数据以及邻域评分工具G-NEST来确定乳腺表达基因的邻域。通过ChIP-Seq方法鉴定了哺乳期间小鼠乳腺和肝组织中组蛋白修饰H3K36me3、H3K4me2和H3K27me3的开放和关闭染色质区域。我们发现，与肝组织相比，泌乳乳腺中独特活性染色质区域的基因邻域极其罕见。相反，大多数邻域的基因在哺乳期间被抑制，这反映在它们的表达水平和它们在沉默染色质区域的位置上。在哺乳期间，染色质沉默在很大程度上在肝脏和乳腺之间共享，而区分乳腺的主要是一小部分组织特异性的分离表达基因。这些发现表明，邻域组织的一个优势是通过染色质抑制的共同机制对基因群进行集体抑制。对乳腺独特性至关重要的基因与邻近的基因隔离开来，可能对表达变化的容忍度较低，而这些基因与负责生物体生存的基因具有相同的特性。
Even in genomes lacking operons, a gene's position in the genome influences its potential for expression. The mechanisms by which adjacent genes are co-expressed are still not completely understood. Using lactation and the mammary gland as a model system, we explore the hypothesis that chromatin state contributes to the co-regulation of gene neighborhoods. The mammary gland represents a unique evolutionary model, due to its recent appearance, in the context of vertebrate genomes. An understanding of how the mammary gland is regulated to produce milk is also of biomedical and agricultural importance for human lactation and dairying. Here, we integrate epigenomic and transcriptomic data to develop a comprehensive regulatory model. Neighborhoods of mammary-expressed genes were determined using expression data derived from pregnant and lactating mice and a neighborhood scoring tool, G-NEST. Regions of open and closed chromatin were identified by ChIP-Seq of histone modifications H3K36me3, H3K4me2, and H3K27me3 in the mouse mammary gland and liver tissue during lactation. We found that neighborhoods of genes in regions of uniquely active chromatin in the lactating mammary gland, compared with liver tissue, were extremely rare. Rather, genes in most neighborhoods were suppressed during lactation as reflected in their expression levels and their location in regions of silenced chromatin. Chromatin silencing was largely shared between the liver and mammary gland during lactation, and what distinguished the mammary gland was mainly a small tissue-specific repertoire of isolated, expressed genes. These findings suggest that an advantage of the neighborhood organization is in the collective repression of groups of genes via a shared mechanism of chromatin repression. Genes essential to the mammary gland's uniqueness are isolated from neighbors, and likely have less tolerance for variation in expression, properties they share with genes responsible for an organism's survival.
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影响因子：
--
作者：
Lemay, Danielle G;Neville, Margaret C;Rudolph, Michael C;Pollard, Katherine S;German, J Bruce
通讯作者：
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14.9
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通讯作者：
Searle SM
Cinteny：多种生物体中同步和基因组重排的灵活分析和可视化。
影响因子：
3
作者：
通讯作者：
--
影响因子：
3
作者：
Lemay, Danielle G.;Martin, William F.;Pollard, Katherine S.
通讯作者：
Pollard, Katherine S.