Global Developmental Gene Programing Involves a Nuclear Form of Fibroblast Growth Factor Receptor-1 (FGFR1).
Global Developmental Gene Programing Involves a Nuclear Form of Fibroblast Growth Factor Receptor-1 (FGFR1).
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DOI：
10.1371/journal.pone.0123380
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Stachowiak MK
中科院分区：
文献类型：
--
作者：
Terranova C;Narla ST;Lee YW;Bard J;Parikh A;Stachowiak EK;Tzanakakis ES;Buck MJ;Birkaya B;Stachowiak MK
遗传学研究已经将Fgfr 1基因置于使原肠胚形成、组织发育和器官发生成为可能的主要个体发育途径的顶端。使用全基因组测序和功能丧失和获得实验，本研究揭示了一种机制，该机制是FGFR 1核形式的全局和直接基因调控的基础，确保多能胚胎干细胞响应于视黄酸分化为神经元细胞。核FGFR 1，无论是单独还是与其伴侣核受体RXR和Nur 77，靶向成千上万的活性基因，并控制多能性，同源框，神经元和中胚层基因的表达。核FGFR 1靶向以Wnt/β-catenin、CREB、BMP、细胞周期和癌症相关TP 53通路、神经外胚层和中胚层编程网络、轴突生长和突触可塑性通路为代表的发育通路中的基因。核FGFR 1靶向已知参与CREB结合蛋白的转录因子的共有序列，CREB结合蛋白是一种常见的转录共调节因子，是核FGFR 1的已建立的结合伴侣。这项研究揭示了核FGFR 1作为细胞，神经和肌肉发育的全球基因组程序员的作用。
Genetic studies have placed the Fgfr1 gene at the top of major ontogenic pathways that enable gastrulation, tissue development and organogenesis. Using genome-wide sequencing and loss and gain of function experiments the present investigation reveals a mechanism that underlies global and direct gene regulation by the nuclear form of FGFR1, ensuring that pluripotent Embryonic Stem Cells differentiate into Neuronal Cells in response to Retinoic Acid. Nuclear FGFR1, both alone and with its partner nuclear receptors RXR and Nur77, targets thousands of active genes and controls the expression of pluripotency, homeobox, neuronal and mesodermal genes. Nuclear FGFR1 targets genes in developmental pathways represented by Wnt/β-catenin, CREB, BMP, the cell cycle and cancer-related TP53 pathway, neuroectodermal and mesodermal programing networks, axonal growth and synaptic plasticity pathways. Nuclear FGFR1 targets the consensus sequences of transcription factors known to engage CREB-binding protein, a common coregulator of transcription and established binding partner of nuclear FGFR1. This investigation reveals the role of nuclear FGFR1 as a global genomic programmer of cell, neural and muscle development.
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影响因子：
64.5
作者：
Goldberg AD;Banaszynski LA;Noh KM;Lewis PW;Elsaesser SJ;Stadler S;Dewell S;Law M;Guo X;Li X;Wen D;Chapgier A;DeKelver RC;Miller JC;Lee YL;Boydston EA;Holmes MC;Gregory PD;Greally JM;Rafii S;Yang C;Scambler PJ;Garrick D;Gibbons RJ;Higgs DR;Cristea IM;Urnov FD;Zheng D;Allis CD
通讯作者：
Allis CD
影响因子：
2.9
作者：
GONZALEZ, AM;BERRY, M;BAIRD, A
通讯作者：
BAIRD, A
影响因子：
10.5
作者：
Abu-Abed, S;Dollé, P;Petkovich, M
通讯作者：
Petkovich, M
影响因子：
64.5
作者：
Ballas, N;Grunseich, C;Mandel, G
通讯作者：
Mandel, G
影响因子：
2.9
作者：
Kehoe, Daniel E.;Lock, Lye T.;Tzanakakis, Emmanuel S.
通讯作者：
Tzanakakis, Emmanuel S.