Abstract
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.
Highlights
Many transcription factors (TFs) involved in vertebrate embryogenesis are expressed across relatively large time windows that encompass a variety of cellular and morphological changes
TALE factors play a key role in early vertebrate embryogenesis, as evidenced by the phenotypes observed in TALE loss-of-function animals
A shared role for TALE and NF-Y factors in controlling H3K27ac may be broadly relevant at the blastula stage, since we find that TALE peaks with adjacent CCAAT motifs are generally associated with higher levels of H3K27ac and lower levels of H3K27me3 than TALE peaks that lack a nearby CCAAT box (Figure 7—figure supplement 1C)
Summary
Many transcription factors (TFs) involved in vertebrate embryogenesis are expressed across relatively large time windows that encompass a variety of cellular and morphological changes. Disruption of the earliest expressed TALE genes in zebrafish (prep1.1, pbx and pbx4) produces severe embryonic defects (Deflorian et al, 2004; Waskiewicz et al, 2002; Popperl et al, 2000) In spite of their function having been defined primarily at gastrula/segmentation stages, TALE factors are present throughout embryogenesis. We find that maternally deposited TALE factors primarily occupy a 10 bp DECA motif at blastula stages This motif was previously identified as a binding site for Prep:Pbx dimers (Chang et al, 1997; Knoepfler and Kamps, 1997; De Kumar et al, 2017; Laurent et al, 2015; Penkov et al, 2013), but was not assigned a biological role. TALE TFs control an anterior gene network throughout zebrafish embryogenesis, but do so by employing distinct DNA motifs and protein partners at different embryonic stages
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