Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, United States.
Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom.
Elife. 2018 Jun 18;7:e36144. doi: 10.7554/eLife.36144.
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.
TALE 因子在胚胎期广泛表达，已知在原肠胚/分节阶段与转录因子（TFs）如 Hox 蛋白形成复合物发挥作用，但尚不清楚是否普遍表达的因子在整个胚胎发生过程中通过相同的机制发挥作用。我们确定了一个 TALE 依赖性的基因调控网络（GRN），该网络对于前部发育是必需的，并在整个胚胎发生过程中检测到与该 GRN 相关的 TALE 占据。在囊胚阶段，我们揭示了 TALE 因子的一种新的功能模式，即它们与附近的 NF-Y 位点占据基因组 DECA 基序。我们证明 TALE 和 NF-Y 形成复合物，并调节该 GRN 基因的染色质状态。在分节阶段，与 GRN 相关的 TALE 占据范围扩大到包括 PBX:HOX 位点附近的 HEXA 基序。因此，TALE 因子控制着一个关键的 GRN，但在不同阶段使用不同的 DNA 基序和蛋白伴侣——这种策略也可能解释它们的致癌潜力，并可能被其他广泛表达的 TFs 采用。
