Differential binding and co-binding pattern of FOXA1 and FOXA3 and their relation to H3K4me3 in HepG2 cells revealed by ChIP-seq.

Differential binding and co-binding pattern of FOXA1 and FOXA3 and their relation to H3K4me3 in HepG2 cells revealed by ChIP-seq.
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ChIP-seq 揭示的 FOXA1 和 FOXA3 在 HepG2 细胞中的差异结合和共结合模式及其与 H3K4me3 的关系。

DOI:
10.1186/gb-2009-10-11-r129
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发表时间:
2009
期刊:
影响因子:
12.3
通讯作者:
Wadelius C
Wadelius C
中科院分区:
生物学1区
文献类型:
--
作者:
Motallebipour M;Ameur A;Reddy Bysani MS;Patra K;Wallerman O;Mangion J;Barker MA;McKernan KJ;Komorowski J;Wadelius C

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HepG2细胞中的FOXA 1和FOXA 3结合模式,以及它们与FOXA 2和彼此之间可能的分子相互作用,通过ChIP-seq揭示。叉头盒/翼状螺旋家族成员FOXA 1、FOXA 2和FOXA 3在肝谱系的发育和特化以及肝特异性基因的持续表达中具有高度重要性。在这里,我们提出了一个全基因组的FOXA 1和FOXA 3结合位点的位置分析在HepG2细胞通过染色质免疫沉淀检测测序(ChIP-seq)研究,并比较这些与我们以前的结果FOXA 2。我们发现,这些因子通常以不同的组合彼此紧密结合,并且染色质的连续免疫沉淀一个,然后是第二个因子(ChIP-reChIP)表明,这发生在同一细胞和同一DNA分子上,表明分子相互作用。使用免疫共沉淀,我们进一步表明,FOXA 2与FOXA 1和FOXA 3在体内相互作用,而FOXA 1和FOXA 3似乎没有相互作用。此外,我们检测到组蛋白H3(H3K4me3)上赖氨酸4在转录起始位点的三甲基化的不同模式,以及FOXA结合位点的这种修饰的方向性。使用多态性位置处的序列读段,我们能够预测FOXA 1、FOXA 3和H3K4me3的等位基因特异性结合。最后,在富集区定位了几个与疾病和数量性状相关的SNPs。我们发现ChIP-seq不仅可以用于创建基因调控图谱,还可以用于预测分子相互作用,并为常见的定量变异机制提供信息。
FOXA1 and FOXA3 binding patterns in HepG2 cells, together with their possible molecular interactions with FOXA2 and each other, are revealed by ChIP-seq. The forkhead box/winged helix family members FOXA1, FOXA2, and FOXA3 are of high importance in development and specification of the hepatic linage and the continued expression of liver-specific genes. Here, we present a genome-wide location analysis of FOXA1 and FOXA3 binding sites in HepG2 cells through chromatin immunoprecipitation with detection by sequencing (ChIP-seq) studies and compare these with our previous results on FOXA2. We found that these factors often bind close to each other in different combinations and consecutive immunoprecipitation of chromatin for one and then a second factor (ChIP-reChIP) shows that this occurs in the same cell and on the same DNA molecule, suggestive of molecular interactions. Using co-immunoprecipitation, we further show that FOXA2 interacts with both FOXA1 and FOXA3 in vivo, while FOXA1 and FOXA3 do not appear to interact. Additionally, we detected diverse patterns of trimethylation of lysine 4 on histone H3 (H3K4me3) at transcriptional start sites and directionality of this modification at FOXA binding sites. Using the sequence reads at polymorphic positions, we were able to predict allele specific binding for FOXA1, FOXA3, and H3K4me3. Finally, several SNPs associated with diseases and quantitative traits were located in the enriched regions. We find that ChIP-seq can be used not only to create gene regulatory maps but also to predict molecular interactions and to inform on the mechanisms for common quantitative variation.
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