A multiple super-enhancer region establishes inter-TAD interactions and controls Hoxa function in cranial neural crest - Archive ouverte HAL Access content directly
Journal Articles Nature Communications Year : 2023

A multiple super-enhancer region establishes inter-TAD interactions and controls Hoxa function in cranial neural crest

Sandra Kessler
  • Function : Author
Maryline Minoux
  • Function : Author
  • PersonId : 1098580
Onkar Joshi
  • Function : Author
Sebastien Ducret
  • Function : Author
Fiona Ross
  • Function : Author
Nathalie Vilain
  • Function : Author
Adwait Salvi
  • Function : Author
Joachim Wolff
  • Function : Author
Hubertus Kohler
  • Function : Author
Michael B. Stadler
  • Function : Author
Filippo M. Rijli
  • Function : Author

Abstract

Enhancer-promoter interactions preferentially occur within boundary-insulated topologically associating domains (TADs), limiting inter-TAD interactions. Enhancer clusters in linear proximity, termed super-enhancers (SEs), ensure high target gene expression levels. Little is known about SE topological regulatory impact during craniofacial development. Here, we identify 2232 genome-wide putative SEs in mouse cranial neural crest cells (CNCCs), 147 of which target genes establishing CNCC positional identity during face formation. In second pharyngeal arch (PA2) CNCCs, a multiple SE-containing region, partitioned into Hoxa Inter-TAD Regulatory Element 1 and 2 (HIRE1 and HIRE2), establishes long-range inter-TAD interactions selectively with Hoxa2, that is required for external and middle ear structures. HIRE2 deletion in a Hoxa2 haploinsufficient background results in microtia. HIRE1 deletion phenocopies the full homeotic Hoxa2 knockout phenotype and induces PA3 and PA4 CNCC abnormalities correlating with Hoxa2 and Hoxa3 transcriptional downregulation. Thus, SEs can overcome TAD insulation and regulate anterior Hoxa gene collinear expression in a CNCC subpopulation-specific manner during craniofacial development.
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Dates and versions

hal-04238114 , version 1 (11-10-2023)

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Sandra Kessler, Maryline Minoux, Onkar Joshi, Yousra Ben Zouari, Sebastien Ducret, et al.. A multiple super-enhancer region establishes inter-TAD interactions and controls Hoxa function in cranial neural crest. Nature Communications, 2023, 14 (1), ⟨10.1038/s41467-023-38953-0⟩. ⟨hal-04238114⟩
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