A multiple super-enhancer region establishes inter-TAD interactions and controls Hoxa function in cranial neural crest
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 t...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-06-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-38953-0 |
| _version_ | 1797806677295104000 |
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| author | Sandra Kessler Maryline Minoux Onkar Joshi Yousra Ben Zouari Sebastien Ducret Fiona Ross Nathalie Vilain Adwait Salvi Joachim Wolff Hubertus Kohler Michael B. Stadler Filippo M. Rijli |
| author_facet | Sandra Kessler Maryline Minoux Onkar Joshi Yousra Ben Zouari Sebastien Ducret Fiona Ross Nathalie Vilain Adwait Salvi Joachim Wolff Hubertus Kohler Michael B. Stadler Filippo M. Rijli |
| author_sort | Sandra Kessler |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-13T06:10:55Z |
| format | Article |
| id | doaj.art-e60e6bd64d4f4787a3c05f67bfcdbdd2 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-13T06:10:55Z |
| publishDate | 2023-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-e60e6bd64d4f4787a3c05f67bfcdbdd22023-06-11T11:18:58ZengNature PortfolioNature Communications2041-17232023-06-0114112210.1038/s41467-023-38953-0A multiple super-enhancer region establishes inter-TAD interactions and controls Hoxa function in cranial neural crestSandra Kessler0Maryline Minoux1Onkar Joshi2Yousra Ben Zouari3Sebastien Ducret4Fiona Ross5Nathalie Vilain6Adwait Salvi7Joachim Wolff8Hubertus Kohler9Michael B. Stadler10Filippo M. Rijli11Friedrich Miescher Institute for Biomedical ResearchFriedrich Miescher Institute for Biomedical ResearchFriedrich Miescher Institute for Biomedical ResearchFriedrich Miescher Institute for Biomedical ResearchFriedrich Miescher Institute for Biomedical ResearchFriedrich Miescher Institute for Biomedical ResearchFriedrich Miescher Institute for Biomedical ResearchFriedrich Miescher Institute for Biomedical ResearchFriedrich Miescher Institute for Biomedical ResearchFriedrich Miescher Institute for Biomedical ResearchFriedrich Miescher Institute for Biomedical ResearchFriedrich Miescher Institute for Biomedical ResearchAbstract 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.https://doi.org/10.1038/s41467-023-38953-0 |
| spellingShingle | Sandra Kessler Maryline Minoux Onkar Joshi Yousra Ben Zouari Sebastien Ducret Fiona Ross Nathalie Vilain Adwait Salvi Joachim Wolff Hubertus Kohler Michael B. Stadler Filippo M. Rijli A multiple super-enhancer region establishes inter-TAD interactions and controls Hoxa function in cranial neural crest Nature Communications |
| title | A multiple super-enhancer region establishes inter-TAD interactions and controls Hoxa function in cranial neural crest |
| title_full | A multiple super-enhancer region establishes inter-TAD interactions and controls Hoxa function in cranial neural crest |
| title_fullStr | A multiple super-enhancer region establishes inter-TAD interactions and controls Hoxa function in cranial neural crest |
| title_full_unstemmed | A multiple super-enhancer region establishes inter-TAD interactions and controls Hoxa function in cranial neural crest |
| title_short | A multiple super-enhancer region establishes inter-TAD interactions and controls Hoxa function in cranial neural crest |
| title_sort | multiple super enhancer region establishes inter tad interactions and controls hoxa function in cranial neural crest |
| url | https://doi.org/10.1038/s41467-023-38953-0 |
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