TALE factors use two distinct functional modes to control an essential zebrafish gene expression program.
TALE factors use two distinct functional modes to control an essential zebrafish gene expression program.
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DOI：
10.7554/elife.36144
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发表时间：
2018-06-18
期刊：
影响因子：
7.7
通讯作者：
Sagerström CG
中科院分区：
文献类型：
--
作者：
Ladam F;Stanney W;Donaldson IJ;Yildiz O;Bobola N;Sagerström CG
TALE因子在胚胎中广泛表达，并且已知在原肠胚/分割阶段与转录因子（TF）如Hox蛋白复合起作用，但尚不清楚这些通常表达的因子在整个胚胎发生中是否通过相同的机制起作用。我们确定了一个TALE依赖的基因调控网络（GRN）所需的前发展和检测TALE占用与此GRN在整个胚胎发生。在囊胚阶段，我们发现了TALE因子的一种新的功能模式，它们占据基因组DECA基序与附近的NF-Y位点。我们证明，TALE和NF-Y形成复合物，并调节染色质状态在这个GRN的基因。在分割阶段，GRN相关的TALE占用扩展到包括PBX：HOX位点附近的HEXA基序。因此，TALE因子控制关键的GRN，但在不同阶段利用不同的DNA基序和蛋白质伴侣-这一策略也可以解释其致癌潜力，并且可以被其他广泛表达的TF采用。
TALE factors are broadly expressed embryonically and known to function in complexes with transcription factors (TFs) like Hox proteins at gastrula/segmentation stages, but it is unclear if such generally expressed factors act by the same mechanism throughout embryogenesis. We identify a TALE-dependent gene regulatory network (GRN) required for anterior development and detect TALE occupancy associated with this GRN throughout embryogenesis. At blastula stages, we uncover a novel functional mode for TALE factors, where they occupy genomic DECA motifs with nearby NF-Y sites. We demonstrate that TALE and NF-Y form complexes and regulate chromatin state at genes of this GRN. At segmentation stages, GRN-associated TALE occupancy expands to include HEXA motifs near PBX:HOX sites. Hence, TALE factors control a key GRN, but utilize distinct DNA motifs and protein partners at different stages – a strategy that may also explain their oncogenic potential and may be employed by other broadly expressed TFs.