Krejcí Jana, Uhlírová Radka, Galiová Gabriela, Kozubek Stanislav, Smigová Jana, Bártová Eva
Institute of Biophysics, Academy of Sciences of the Czech Republic, v.v.i., Brno, Czech Republic.
J Cell Physiol. 2009 Jun;219(3):677-87. doi: 10.1002/jcp.21714.
Epigenetic marks are important factors regulating the pluripotency and differentiation of human embryonic stem cells (hESCs). In this study, we analyzed H3K9 acetylation, an epigenetic mark associated with transcriptionally active chromatin, during endoderm-like differentiation of hESCs. ChIP-on-chip analysis revealed that differentiation results in a genome-wide decrease in promoter H3K9 acetylation. Among the 24,659 promoters analyzed, only 117 are likely to be involved in pluripotency, while 25 acetylated promoters are likely to be responsible for endoderm-like differentiation. In pluripotent hESCs, the chromosomes with the highest absolute levels of H3K9 acetylation are chromosomes 1, 6, 2, 17, 11, and 12 (listed in order of decreasing acetylation). Chromosomes 17, 19, 11, 20, 22, and 12 are the most prone to differentiation-related changes (both increased acetylation and deacetylation). When chromosome size (in Mb) was accounted for, the highest H3K9 acetylation levels were found on chromosome 19, 17, 6, 12, 11, and 1, and the greatest differentiation-associated decreases in H3K9 acetylation occurred on chromosomes 19, 17, 11, 12, 16, and 1. The gene density and size of individual chromosomes were strongly correlated with the levels of H3K9 acetylation. Our analyses point to chromosomes 11, 12, 17, and 19 as being critical for hESC pluripotency and endoderm-like differentiation. J. Cell. Physiol. 219: 677-687, 2009. (c) 2009 Wiley-Liss, Inc.
表观遗传标记是调节人类胚胎干细胞（hESC）多能性和分化的重要因素。在本研究中，我们分析了hESC向类内胚层分化过程中与转录活性染色质相关的表观遗传标记H3K9乙酰化。芯片免疫沉淀分析表明，分化导致全基因组范围内启动子H3K9乙酰化水平降低。在分析的24,659个启动子中，只有117个可能与多能性有关，而25个乙酰化启动子可能与类内胚层分化有关。在多能性hESC中，H3K9乙酰化绝对水平最高的染色体是1号、6号、2号、17号、11号和12号染色体（按乙酰化水平降低顺序列出）。17号、19号、11号、20号、22号和12号染色体最容易发生与分化相关的变化（乙酰化增加和去乙酰化）。当考虑染色体大小（以兆碱基计）时，H3K9乙酰化水平最高的是19号、17号、6号、12号、11号和1号染色体，而与分化相关的H3K9乙酰化水平降低幅度最大的是19号、17号、11号、12号、16号和1号染色体。单个染色体的基因密度和大小与H3K9乙酰化水平密切相关。我们的分析表明，11号、12号、17号和19号染色体对hESC多能性和类内胚层分化至关重要。《细胞生理学杂志》2009年第219卷：677 - 687页。（c）2009年威利 - 利斯出版公司。
