Function of GATA factors in the adult mouse liver.
Function of GATA factors in the adult mouse liver.
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DOI：
10.1371/journal.pone.0083723
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Blobel GA
中科院分区：
文献类型：
--
作者：
Zheng R;Rebolledo-Jaramillo B;Zong Y;Wang L;Russo P;Hancock W;Stanger BZ;Hardison RC;Blobel GA
GATA转录因子及其辅助因子FOG控制着多种组织的发育。GATA4和GATA6对胚胎肝芽的扩张至关重要，但它们在成人肝脏中的表达模式和功能尚不清楚。我们对GATA和FOG因子在小鼠全肝和纯化肝细胞中的表达进行了表征。GATA4、GATA6和FOG1是全肝和肝细胞中表达最显著的家族成员。GATA4染色质免疫沉淀和高通量测序（ChIP-seq）鉴定出4409个被占用的位点，这些位点与肝功能相关的本体中富集的基因相关，包括脂质和糖代谢。然而，肝细胞特异性切除Gata4对肝脏总体结构和功能的影响很小，即使在再生应激条件下也是如此，尽管Gata4占据了大量基因，但基因表达的变化相对较小。为了解决GATA4和GATA6之间可能存在的冗余，有条件地切除了这两个因素。令人惊讶的是，Gata4,6的联合缺失并没有加剧Gata4单独缺失所导致的表型。这表明在成人肝细胞中存在一个异常强大的转录网络，以确保肝功能的维持。
GATA transcription factors and their Friend of Gata (FOG) cofactors control the development of diverse tissues. GATA4 and GATA6 are essential for the expansion of the embryonic liver bud, but their expression patterns and functions in the adult liver are unclear. We characterized the expression of GATA and FOG factors in whole mouse liver and purified hepatocytes. GATA4, GATA6, and FOG1 are the most prominently expressed family members in whole liver and hepatocytes. GATA4 chromatin immunoprecipitation followed by high throughput sequencing (ChIP-seq) identified 4409 occupied sites, associated with genes enriched in ontologies related to liver function, including lipid and glucose metabolism. However, hepatocyte-specific excision of Gata4 had little impact on gross liver architecture and function, even under conditions of regenerative stress, and, despite the large number of GATA4 occupied genes, resulted in relatively few changes in gene expression. To address possible redundancy between GATA4 and GATA6, both factors were conditionally excised. Surprisingly, combined Gata4,6 loss did not exacerbate the phenotype resulting from Gata4 loss alone. This points to the presence of an unusually robust transcriptional network in adult hepatocytes that ensures the maintenance of liver function.
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DOI：
10.1073/pnas.1016959108
发表时间：
2011-04-05
影响因子：
11.1
作者：
He, Aibin;Kong, Sek Won;Pu, William T.
通讯作者：
Pu, William T.
影响因子：
5.3
作者：
Hayhurst, GP;Lee, YH;Gonzalez, FJ
通讯作者：
Gonzalez, FJ
DOI：
10.1126/science.1198125
发表时间：
2011-03-11
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Feng D;Liu T;Sun Z;Bugge A;Mullican SE;Alenghat T;Liu XS;Lazar MA
通讯作者：
Lazar MA
影响因子：
3.5
作者：
Denson, LA;McClure, MH;Jacobs, HC
通讯作者：
Jacobs, HC
影响因子：
16
作者：
Crispino, JD;Lodish, MB;Orkin, SH
通讯作者：
Orkin, SH