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Publication : HOX13-dependent chromatin accessibility underlies the transition towards the digit development program.

First Author  Desanlis I Year  2020
Journal  Nat Commun Volume  11
Issue  1 Pages  2491
PubMed ID  32427842 Mgi Jnum  J:292451
Mgi Id  MGI:6447344 Doi  10.1038/s41467-020-16317-2
Citation  Desanlis I, et al. (2020) HOX13-dependent chromatin accessibility underlies the transition towards the digit development program. Nat Commun 11(1):2491
abstractText  Hox genes encode transcription factors (TFs) that establish morphological diversity in the developing embryo. The similar DNA-binding motifs of the various HOX TFs contrast with the wide-range of HOX-dependent genetic programs. The influence of the chromatin context on HOX binding specificity remains elusive. Here, we used the developing limb as a model system to compare the binding specificity of HOXA13 and HOXD13 (HOX13 hereafter), which are required for digit formation, and HOXA11, involved in forearm/leg development. We find that upon ectopic expression in distal limb buds, HOXA11 binds sites normally HOX13-specific. Importantly, these sites are loci whose chromatin accessibility relies on HOX13. Moreover, we show that chromatin accessibility specific to the distal limb requires HOX13 function. Based on these results, we propose that HOX13 TFs pioneer the distal limb-specific chromatin accessibility landscape for the proper implementation of the distal limb developmental program.
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