HOX13 factors shape cell developmental transcriptional program through multiple mechanisms that regulate chromatin accessibility.
HOX transcription factors pattern embryonic tissues and organs and have post-developmental roles in adult tissue maintenance and function. They can bind inaccessible chromatin, but their roles in chromatin accessibility remain unclear. Using in vivo and in vitro approaches, we show that HOX13 factors promote both initial opening and maintenance of accessibility at subsets of target regulatory…
HOX13 factors play a crucial role in shaping the developmental transcriptional program of cells through various mechanisms that regulate chromatin accessibility. These factors can bind to inaccessible chromatin, but their specific roles in chromatin accessibility are not yet fully understood. By utilizing in vivo and in vitro techniques, researchers have found that HOX13 factors contribute to both the initial opening and the maintenance of accessibility at certain target regulatory elements.
This regulation occurs through a combination of the factors' homodimerization and their ability to recruit the SWI/SNF chromatin remodeling complex. The study reveals that while SWI/SNF aids in the extent of chromatin opening, it is neither the sole determinant nor sufficient for HOXA13's pioneering activity. In induced pluripotent stem cells (iPSCs), the induction of HOXA13 leads to a rapid decrease in the expression of pluripotency genes and an activation of an early osteochondrogenic transcriptional program.
This response is believed to be at least partially due to the direct regulation of genes by HOXA13. Overall, the findings demonstrate that HOX13 factors have multiple, context-dependent contributions to chromatin regulation, leading to early lineage-specific responses.
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