GATA-1 genome-wide occupancy associates with distinct epigenetic profiles in mouse fetal liver erythropoiesis.
GATA-1 genome-wide occupancy associates with distinct epigenetic profiles in mouse fetal liver erythropoiesis.
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DOI：
10.1093/nar/gkt167
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发表时间：
2013-05
影响因子：
14.9
通讯作者：
Strouboulis J
中科院分区：
文献类型：
--
作者：
Papadopoulos GL;Karkoulia E;Tsamardinos I;Porcher C;Ragoussis J;Bungert J;Strouboulis J
我们报告了从 E12.5 天小鼠胎儿肝细胞中分离的原红细胞和成熟红系细胞中关键造血转录因子 GATA-1 的基因组占据谱。将 GATA-1 占用谱与胎儿肝细胞中可用的全基因组转录因子和表观遗传谱进行整合，能够评估 GATA-1 在红系分化过程中调节靶基因局部染色质结构的作用。我们的结果表明，GATA-1 优先与特定表观遗传修饰的变化相关，例如 H4K16、H3K27 乙酰化和 H3K4 二甲基化。此外，我们根据原红细胞和成熟胎儿肝源性红细胞的基因组特征，使用随机森林 (RF) 非线性回归来预测 GATA-1 靶基因表达水平的变化。值得注意的是，我们的预测模型解释了 62% 的基因表达变异的高比例。 RF 模型计算的邻近值的分层聚类产生了上调基因与下调基因的清晰分离，以及两个不同组中下调基因的进一步分离。因此，我们对小鼠原代红系细胞中 GATA-1 全基因组占有率及其与全局表观遗传标记的整合的研究揭示了与特定表观遗传特征和功能特征相关的三组 GATA-1 基因靶标。
We report the genomic occupancy profiles of the key hematopoietic transcription factor GATA-1 in pro-erythroblasts and mature erythroid cells fractionated from day E12.5 mouse fetal liver cells. Integration of GATA-1 occupancy profiles with available genome-wide transcription factor and epigenetic profiles assayed in fetal liver cells enabled as to evaluate GATA-1 involvement in modulating local chromatin structure of target genes during erythroid differentiation. Our results suggest that GATA-1 associates preferentially with changes of specific epigenetic modifications, such as H4K16, H3K27 acetylation and H3K4 di-methylation. Furthermore, we used random forest (RF) non-linear regression to predict changes in the expression levels of GATA-1 target genes based on the genomic features available for pro-erythroblasts and mature fetal liver-derived erythroid cells. Remarkably, our prediction model explained a high proportion of 62% of variation in gene expression. Hierarchical clustering of the proximity values calculated by the RF model produced a clear separation of upregulated versus downregulated genes and a further separation of downregulated genes in two distinct groups. Thus, our study of GATA-1 genome-wide occupancy profiles in mouse primary erythroid cells and their integration with global epigenetic marks reveals three clusters of GATA-1 gene targets that are associated with specific epigenetic signatures and functional characteristics.
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影响因子：
6.5
作者：
Kina, T;Ikuta, K;Katsura, Y
通讯作者：
Katsura, Y
影响因子：
16
作者：
Fujiwara T;O'Geen H;Keles S;Blahnik K;Linnemann AK;Kang YA;Choi K;Farnham PJ;Bresnick EH
通讯作者：
Bresnick EH
影响因子：
8
作者：
Cantor, AB;Orkin, SH
通讯作者：
Orkin, SH
影响因子：
4
作者：
Magnusdottir, Erna;Gillich, Astrid;Surani, M. Azim
通讯作者：
Surani, M. Azim
影响因子：
11.4
作者：
MacQuarrie, Kyle L.;Fong, Abraham P.;Morse, Randall H.;Tapscott, Stephen J.
通讯作者：
Tapscott, Stephen J.