Broad shifts in gene expression during early postnatal life are associated with shifts in histone methylation patterns.
Broad shifts in gene expression during early postnatal life are associated with shifts in histone methylation patterns.
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DOI：
10.1371/journal.pone.0086957
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Baron J
中科院分区：
文献类型：
--
作者：
Lui JC;Chen W;Cheung CS;Baron J
在出生后早期，基因表达的广泛变化伴随着多个主要器官发生，表明存在一个共同的核心发育遗传程序。该计划包括数百个生长促进基因，这些基因在肝脏，肾脏，肺和心脏中随着年龄的增长而下调，并且有证据表明，该计划的这一组成部分驱动了青少年生活中发生的细胞增殖的广泛下降，因为器官接近成人大小。为了研究可能协调该程序的表观遗传变化，我们进行了染色质免疫沉淀-启动子平铺阵列，以评估组蛋白H3 K4和H3 K27三甲基化（me 3）在整个肾脏和肺基因组启动子区域的时间变化，比较1至4周龄小鼠。我们发现H3 K4 me 3和H3 K27 me 3在肾脏和肺中随着年龄的增长而发生广泛的全基因组变化。在两个器官中具有一致性变化的基因数量远远大于偶然预期。通过微阵列评估，H3 K4 me 3的时间变化与基因表达的变化表现出强烈的正相关，而H3 K27 me 3的变化表现出负相关。基因本体分析表明，特定组蛋白甲基化标记的变化与特定的发育功能有关。特别令人感兴趣的是，在两个器官中H3 K4 me 3随着年龄的增长而减少的基因强烈地涉及细胞周期和细胞增殖功能。总之，研究结果表明，在青少年生活中发生在多个器官中的基因表达的共同核心发育程序与组蛋白甲基化的共同核心发育程序相关。特别是，下降的H3 K4 me 3与基因下调密切相关，并发生在许多生长调节基因的启动子区域，这表明组蛋白甲基化的这种变化可能有助于推动青少年身体生长减速的遗传程序的组成部分。
During early postnatal life, extensive changes in gene expression occur concomitantly in multiple major organs, indicating the existence of a common core developmental genetic program. This program includes hundreds of growth-promoting genes that are downregulated with age in liver, kidney, lung, and heart, and there is evidence that this component of the program drives the widespread decline in cell proliferation that occurs in juvenile life, as organs approach adult sizes. To investigate epigenetic changes that might orchestrate this program, we performed chromatin immunoprecipitation-promoter tiling array to assess temporal changes in histone H3K4 and H3K27 trimethylation (me3) at promoter regions throughout the genome in kidney and lung, comparing 1- to 4-wk-old mice. We found extensive genome-wide shifts in H3K4me3 and H3K27me3 occurring with age in both kidney and lung. The number of genes with concordant changes in the two organs was far greater than expected by chance. Temporal changes in H3K4me3 showed a strong, positive association with changes in gene expression, assessed by microarray, whereas changes in H3K27me3 showed a negative association. Gene ontology analysis indicated that shifts in specific histone methylation marks were associated with specific developmental functions. Of particular interest, genes with decreases in H3K4me3 with age in both organs were strongly implicated in cell cycle and cell proliferation functions. Taken together, the findings suggest that the common core developmental program of gene expression which occurs in multiple organs during juvenile life is associated with a common core developmental program of histone methylation. In particular, declining H3K4me3 is strongly associated with gene downregulation and occurs in the promoter regions of many growth-regulating genes, suggesting that this change in histone methylation may contribute to the component of the genetic program that drives juvenile body growth deceleration.
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影响因子：
64.5
作者：
Gifford CA;Ziller MJ;Gu H;Trapnell C;Donaghey J;Tsankov A;Shalek AK;Kelley DR;Shishkin AA;Issner R;Zhang X;Coyne M;Fostel JL;Holmes L;Meldrim J;Guttman M;Epstein C;Park H;Kohlbacher O;Rinn J;Gnirke A;Lander ES;Bernstein BE;Meissner A
通讯作者：
Meissner A
影响因子：
64.5
作者：
Guenther, Matthew G.;Levine, Stuart S.;Young, Richard A.
通讯作者：
Young, Richard A.
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影响因子：
5
作者：
Huang, Y.;Min, S.;Yang, R.
通讯作者：
Yang, R.
影响因子：
8.8
作者：
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影响因子：
4.8
作者：
Finkielstain, Gabriela P.;Forcinito, Patricia;Baron, Jeffrey
通讯作者：
Baron, Jeffrey