Cross species comparison of C/EBPα and PPARγ profiles in mouse and human adipocytes reveals interdependent retention of binding sites.
Cross species comparison of C/EBPα and PPARγ profiles in mouse and human adipocytes reveals interdependent retention of binding sites.
复制标题
DOI：
10.1186/1471-2164-12-152
复制
发表时间：
2011-03-16
期刊：
影响因子：
4.4
通讯作者：
Mandrup S
中科院分区：
文献类型：
--
作者：
Schmidt SF;Jørgensen M;Chen Y;Nielsen R;Sandelin A;Mandrup S
转录因子过氧化物酶体增殖物激活受体γ（peroxisome proliferator activated receptor γ，PPARγ）和CCAAT/增强子结合蛋白α（enhancer binding protein α，C/EBPα）是脂肪细胞分化和功能的关键转录调控因子。我们和其他人以前已经表明，这两个转录因子的结合位点显示出高度的重叠，并与大多数基因在小鼠3 T3-L1脂肪细胞分化过程中上调。在这里，我们绘制了人SGBS脂肪细胞中C/EBPα和PPARγ的所有结合位点，并将其与小鼠脂肪细胞的全基因组图谱进行了比较，以系统地研究小鼠和人之间与原位区域中位点保留相关的生物学特征。尽管结合位点的物种间保留有限，但几种生物学特征使位点更有可能被保留。首先，小鼠中的PPARγ和C/EBPα的共结合是人体中相应结合位点保留的最有力预测因素。其次，在脂肪形成过程中高度上调的基因附近显著增加保留。第三，C/EBPα共有位点的存在与两种因子的保留相关，表明C/EBPα促进了PPARγ的募集。第四，保留与结合区域内的整体序列保守性相关，与C/EBPα和PPARγ序列模式无关，表明其他转录因子与这两个关键转录因子协同工作。这项研究提供了一个全面和系统的分析，什么生物学特性的影响保留的结合位点之间的人和小鼠。具体来说，我们发现C/EBPα和PPARγ在脂肪细胞中的结合以高度相互依赖的方式进化，表明这两种转录因子之间存在显著的协同性。
The transcription factors peroxisome proliferator activated receptor γ (PPARγ) and CCAAT/enhancer binding protein α (C/EBPα) are key transcriptional regulators of adipocyte differentiation and function. We and others have previously shown that binding sites of these two transcription factors show a high degree of overlap and are associated with the majority of genes upregulated during differentiation of murine 3T3-L1 adipocytes. Here we have mapped all binding sites of C/EBPα and PPARγ in human SGBS adipocytes and compared these with the genome-wide profiles from mouse adipocytes to systematically investigate what biological features correlate with retention of sites in orthologous regions between mouse and human. Despite a limited interspecies retention of binding sites, several biological features make sites more likely to be retained. First, co-binding of PPARγ and C/EBPα in mouse is the most powerful predictor of retention of the corresponding binding sites in human. Second, vicinity to genes highly upregulated during adipogenesis significantly increases retention. Third, the presence of C/EBPα consensus sites correlate with retention of both factors, indicating that C/EBPα facilitates recruitment of PPARγ. Fourth, retention correlates with overall sequence conservation within the binding regions independent of C/EBPα and PPARγ sequence patterns, indicating that other transcription factors work cooperatively with these two key transcription factors. This study provides a comprehensive and systematic analysis of what biological features impact on retention of binding sites between human and mouse. Specifically, we show that the binding of C/EBPα and PPARγ in adipocytes have evolved in a highly interdependent manner, indicating a significant cooperativity between these two transcription factors.
登录
查看更多内容
影响因子：
7.7
作者：
Boj SF;Servitja JM;Martin D;Rios M;Talianidis I;Guigo R;Ferrer J
通讯作者：
Ferrer J
DOI：
10.1126/science.1183621
发表时间：
2010-04-09
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Kasowski M;Grubert F;Heffelfinger C;Hariharan M;Asabere A;Waszak SM;Habegger L;Rozowsky J;Shi M;Urban AE;Hong MY;Karczewski KJ;Huber W;Weissman SM;Gerstein MB;Korbel JO;Snyder M
通讯作者：
Snyder M
影响因子：
30.8
作者：
Kunarso, Galih;Chia, Na-Yu;Bourque, Guillaume
通讯作者：
Bourque, Guillaume
影响因子：
10.5
作者：
Rosen, ED;Hsu, CH;Spiegelman, BM
通讯作者：
Spiegelman, BM
影响因子：
16
作者：
Barak, Y;Nelson, MC;Evans, RM
通讯作者：
Evans, RM