Adwait Salvi

Friedrich Miescher Institute

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Fiona Ross

Karolinska Institutet

Maryline Minoux

Friedrich Miescher Institute

Sébastien Ducret

Friedrich Miescher Institute

Yousra Ben Zouari

Institut de génétique et de biologie moléculaire et cellulaire

Hubertus Kohler

Friedrich Miescher Institute

Sandra Kessler

Friedrich Miescher Institute

Nathalie Vilain

Friedrich Miescher Institute

Filippo M. Rijli

Friedrich Miescher Institute

Onkar Joshi

University of Utah

Joachim Wolff

Institut für Arbeitsmarkt und Berufsforschung

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Friedrich Miescher Institute

Centre National de la Recherche Scientifique

Institut de génétique et de biologie moléculaire et cellulaire

Université de Strasbourg

Inserm

Institut de Biologie Moléculaire et Cellulaire

Novartis (Switzerland)

University of Basel

Karolinska Institutet

Kingston University

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

Nature Communications (2023)

Sandra Kessler Maryline Minoux Onkar Joshi Yousra Ben Zouari Sébastien Ducret

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.

Cranial neural crest

Haploinsufficiency

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10.1038/s41467-023-38953-0

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Citations (11)