Isl1 and Pou4f2 form a complex to regulate target genes in developing retinal ganglion cells.
Isl1 and Pou4f2 form a complex to regulate target genes in developing retinal ganglion cells.
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DOI：
10.1371/journal.pone.0092105
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Mu X
中科院分区：
文献类型：
--
作者：
Li R;Wu F;Ruonala R;Sapkota D;Hu Z;Mu X
在包括发育在内的生物过程中，基因表达的精确调控通常是通过多种转录因子的组合作用来实现的。这些因素相互作用的机制在很大程度上尚不清楚。我们以前已经表明，Isl 1，Lim-Homedomain转录因子，和Pou 4f 2，IV类POU结构域转录因子，共调节视网膜神经节细胞（RGC）分化所需的一组基因。在这里，我们进一步探讨这两个因素如何相互作用，以精确地调节RGC发展过程中的基因表达。通过GST下拉测定、免疫共沉淀和电泳迁移率变化测定，我们表明Isl 1和Pou 4f 2在体外和体内形成复合物，并鉴定了这两种蛋白质中负责这种相互作用的结构域。通过荧光素酶测定、原位杂交和RNA-seq，我们进一步证明了这两个因素对发育中的RGC中的基因表达有定量贡献。虽然每种因子单独都可以激活基因表达，但这两种因子都需要达到最佳表达水平。最后，我们发现Isl 1和Pou 4f 2可以分别与其他POU和Lim-Homeodomain因子相互作用，表明这两类转录因子之间的相互作用在发育和其他生物过程中是普遍存在的。
Precise regulation of gene expression during biological processes, including development, is often achieved by combinatorial action of multiple transcription factors. The mechanisms by which these factors collaborate are largely not known. We have shown previously that Isl1, a Lim-Homeodomain transcription factor, and Pou4f2, a class IV POU domain transcription factor, co-regulate a set of genes required for retinal ganglion cell (RGC) differentiation. Here we further explore how these two factors interact to precisely regulate gene expression during RGC development. By GST pulldown assays, co-immunoprecipitation, and electrophoretic mobility shift assays, we show that Isl1 and Pou4f2 form a complex in vitro and in vivo, and identify the domains within these two proteins that are responsible for this interaction. By luciferase assay, in situ hybridization, and RNA-seq, we further demonstrate that the two factors contribute quantitatively to gene expression in the developing RGCs. Although each factor alone can activate gene expression, both factors are required to achieve optimal expression levels. Finally, we discover that Isl1 and Pou4f2 can interact with other POU and Lim-Homeodomain factors respectively, indicating the interactions between these two classes of transcription factors are prevalent in development and other biological processes.
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影响因子：
4.5
作者：
Hao H;Kim DS;Klocke B;Johnson KR;Cui K;Gotoh N;Zang C;Gregorski J;Gieser L;Peng W;Fann Y;Seifert M;Zhao K;Swaroop A
通讯作者：
Swaroop A
影响因子：
10.5
作者：
Jacobson, EM;Li, P;Aggarwal, AK
通讯作者：
Aggarwal, AK
DOI：
10.1073/pnas.92.7.2720
发表时间：
1995-03-28
影响因子：
11.1
作者：
BACH, I;RHODES, SJ;ROSENFELD, MG
通讯作者：
ROSENFELD, MG
影响因子：
2.7
作者：
Gan, L;Wang, SW;Klein, WH
通讯作者：
Klein, WH
DOI：
10.1073/pnas.0802627105
发表时间：
2008-05-13
影响因子：
11.1
作者：
Mu, Xiuqian;Fu, Xueyao;Klein, William H.
通讯作者：
Klein, William H.