Differential abilities to engage inaccessible chromatin diversify vertebrate Hox binding patterns

Milica Bulajić, Divyanshi Srivastava, Jeremy S. Dasen, Hynek Wichterle, Shaun Mahony, Esteban O. Mazzoni

Research output: Contribution to journalArticlepeer-review

Abstract

Although Hox genes encode for conserved transcription factors (TFs), they are further divided into anterior, central and posterior groups based on their DNA-binding domain similarity. The posterior Hox group expanded in the deuterostome clade and patterns caudal and distal structures. We aimed to address how similar Hox TFs diverge to induce different positional identities. We studied Hox TF DNA-binding and regulatory activity during an in vitro motor neuron differentiation system that recapitulates embryonic development. We found diversity in the genomic binding profiles of different Hox TFs, even among the posterior group paralogs that share similar DNA-binding domains. These differences in genomic binding were explained by differing abilities to bind to previously inaccessible sites. For example, the posterior group HOXC9 had a greater ability to bind occluded sites than the posterior HOXC10, producing different binding patterns and driving differential gene expression programs. From these results, we propose that the differential abilities of posterior Hox TFs to bind to previously inaccessible chromatin drive patterning diversification.This article has an associated 'The people behind the papers' interview.

Original languageEnglish (US)
JournalDevelopment (Cambridge)
Volume147
Issue number22
DOIs
StatePublished - Nov 23 2020

Keywords

  • Binding
  • Chromatin
  • Hox
  • Patterning
  • Spinal cord
  • Stem cell differentiation

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

Fingerprint Dive into the research topics of 'Differential abilities to engage inaccessible chromatin diversify vertebrate Hox binding patterns'. Together they form a unique fingerprint.

Cite this