Genome-wide profiling of H3K56 acetylation and transcription factor binding sites in human adipocytes.
Genome-wide profiling of H3K56 acetylation and transcription factor binding sites in human adipocytes.
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DOI：
10.1371/journal.pone.0019778
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Fraenkel E
中科院分区：
文献类型：
--
作者：
Lo KA;Bauchmann MK;Baumann AP;Donahue CJ;Thiede MA;Hayes LS;des Etages SA;Fraenkel E
肥胖和代谢疾病的日益流行，要求我们更好地了解脂肪细胞生物学。脂肪细胞中转录的调控尤为重要，因为它是几种治疗方法的靶点。转录结果受组蛋白修饰和转录因子结合的影响。尽管在小鼠3T3 - L1细胞系中已经对几种重要转录因子的表观遗传状态和结合位点进行了分析，但在人类脂肪细胞中却缺乏此类数据。在这项研究中，我们在源自间充质干细胞的人类脂肪细胞中鉴定了H3K56乙酰化位点。H3K56由CBP和p300乙酰化，由SIRT1去乙酰化，它们都是在糖尿病和胰岛素信号传导中具有重要作用的蛋白质。我们发现，虽然几乎一半的基因组显示出H3K56乙酰化的迹象，但H3K56乙酰化水平最高的区域与脂肪因子信号通路和II型糖尿病通路中的转录因子及蛋白质相关。为了发现将乙酰转移酶和去乙酰化酶招募到H3K56乙酰化位点的转录因子，我们分析了H3K56乙酰化区域附近的DNA序列，发现E2F识别序列富集。通过染色质免疫沉淀结合高通量测序，我们证实被E2F4结合的基因，以及被HSF - 1和C/EBPα结合的基因，其H3K56乙酰化水平高于预期，并且转录因子结合位点和乙酰化位点往往相邻但很少重叠。我们还发现C/EBPα在3T3 - L1和人类脂肪细胞中的结合靶点之间存在显著差异，这凸显了构建物种特异性表观遗传和转录因子结合位点图谱的必要性。这是人类脂肪细胞中H3K56乙酰化、E2F4、C/EBPα和HSF - 1结合的首个全基因组图谱，将成为更好地理解脂肪细胞转录调控的重要资源。
The growing epidemic of obesity and metabolic diseases calls for a better understanding of adipocyte biology. The regulation of transcription in adipocytes is particularly important, as it is a target for several therapeutic approaches. Transcriptional outcomes are influenced by both histone modifications and transcription factor binding. Although the epigenetic states and binding sites of several important transcription factors have been profiled in the mouse 3T3-L1 cell line, such data are lacking in human adipocytes. In this study, we identified H3K56 acetylation sites in human adipocytes derived from mesenchymal stem cells. H3K56 is acetylated by CBP and p300, and deacetylated by SIRT1, all are proteins with important roles in diabetes and insulin signaling. We found that while almost half of the genome shows signs of H3K56 acetylation, the highest level of H3K56 acetylation is associated with transcription factors and proteins in the adipokine signaling and Type II Diabetes pathways. In order to discover the transcription factors that recruit acetyltransferases and deacetylases to sites of H3K56 acetylation, we analyzed DNA sequences near H3K56 acetylated regions and found that the E2F recognition sequence was enriched. Using chromatin immunoprecipitation followed by high-throughput sequencing, we confirmed that genes bound by E2F4, as well as those by HSF-1 and C/EBPα, have higher than expected levels of H3K56 acetylation, and that the transcription factor binding sites and acetylation sites are often adjacent but rarely overlap. We also discovered a significant difference between bound targets of C/EBPα in 3T3-L1 and human adipocytes, highlighting the need to construct species-specific epigenetic and transcription factor binding site maps. This is the first genome-wide profile of H3K56 acetylation, E2F4, C/EBPα and HSF-1 binding in human adipocytes, and will serve as an important resource for better understanding adipocyte transcriptional regulation.
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影响因子：
4
作者：
Caton, Paul W.;Nayuni, Nanda K.;Corder, Roger
通讯作者：
Corder, Roger
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DOI：
10.1073/pnas.1016306107
发表时间：
2010-12-14
影响因子：
11.1
作者：
Schwer, Bjoern;Schumacher, Bjoern;Alt, Frederick W.
通讯作者：
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影响因子：
64.5
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通讯作者：
Young RA
影响因子：
3.7
作者：
Conboy, Caitlin M.;Spyrou, Christiana;Thorne, Natalie P.;Wade, Elizabeth J.;Barbosa-Morais, Nuno L.;Wilson, Michael D.;Bhattacharjee, Arindam;Young, Richard A.;Tavare, Simon;Lees, Jacqueline A.;Odom, Duncan T.
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Odom, Duncan T.
影响因子：
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作者：
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通讯作者：
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