A complex regulatory landscape involved in the development of mammalian external genitals
Developmental genes are often controlled by large regulatory landscapes matching topologically associating domains (TADs). In various contexts, the associated chromatin backbone is modified by specific enhancer–enhancer and enhancer–promoter interactions. We used a TAD flanking the mouse HoxD cluste...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2020-04-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/52962 |
| _version_ | 1811201242238550016 |
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| author | Ana Rita Amândio Lucille Lopez-Delisle Christopher Chase Bolt Bénédicte Mascrez Denis Duboule |
| author_facet | Ana Rita Amândio Lucille Lopez-Delisle Christopher Chase Bolt Bénédicte Mascrez Denis Duboule |
| author_sort | Ana Rita Amândio |
| collection | DOAJ |
| description | Developmental genes are often controlled by large regulatory landscapes matching topologically associating domains (TADs). In various contexts, the associated chromatin backbone is modified by specific enhancer–enhancer and enhancer–promoter interactions. We used a TAD flanking the mouse HoxD cluster to study how these regulatory architectures are formed and deconstructed once their function achieved. We describe this TAD as a functional unit, with several regulatory sequences acting together to elicit a transcriptional response. With one exception, deletion of these sequences didn’t modify the transcriptional outcome, a result at odds with a conventional view of enhancer function. The deletion and inversion of a CTCF site located near these regulatory sequences did not affect transcription of the target gene. Slight modifications were nevertheless observed, in agreement with the loop extrusion model. We discuss these unexpected results considering both conventional and alternative explanations relying on the accumulation of poorly specific factors within the TAD backbone. |
| first_indexed | 2024-04-12T02:18:51Z |
| format | Article |
| id | doaj.art-4ff15e207ff54a9bb67ecfd1524b282e |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T02:18:51Z |
| publishDate | 2020-04-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-4ff15e207ff54a9bb67ecfd1524b282e2022-12-22T03:52:11ZengeLife Sciences Publications LtdeLife2050-084X2020-04-01910.7554/eLife.52962A complex regulatory landscape involved in the development of mammalian external genitalsAna Rita Amândio0https://orcid.org/0000-0003-0634-4042Lucille Lopez-Delisle1Christopher Chase Bolt2https://orcid.org/0000-0002-3544-3552Bénédicte Mascrez3Denis Duboule4https://orcid.org/0000-0001-9961-2960School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, SwitzerlandSchool of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, SwitzerlandSchool of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, SwitzerlandDepartment of Genetics and Evolution, University of Geneva, Geneva, SwitzerlandSchool of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland; Department of Genetics and Evolution, University of Geneva, Geneva, Switzerland; Collège de France, Paris, FranceDevelopmental genes are often controlled by large regulatory landscapes matching topologically associating domains (TADs). In various contexts, the associated chromatin backbone is modified by specific enhancer–enhancer and enhancer–promoter interactions. We used a TAD flanking the mouse HoxD cluster to study how these regulatory architectures are formed and deconstructed once their function achieved. We describe this TAD as a functional unit, with several regulatory sequences acting together to elicit a transcriptional response. With one exception, deletion of these sequences didn’t modify the transcriptional outcome, a result at odds with a conventional view of enhancer function. The deletion and inversion of a CTCF site located near these regulatory sequences did not affect transcription of the target gene. Slight modifications were nevertheless observed, in agreement with the loop extrusion model. We discuss these unexpected results considering both conventional and alternative explanations relying on the accumulation of poorly specific factors within the TAD backbone.https://elifesciences.org/articles/52962hox clustersTADCTCFchromatinloop extrusionenhancers |
| spellingShingle | Ana Rita Amândio Lucille Lopez-Delisle Christopher Chase Bolt Bénédicte Mascrez Denis Duboule A complex regulatory landscape involved in the development of mammalian external genitals eLife hox clusters TAD CTCF chromatin loop extrusion enhancers |
| title | A complex regulatory landscape involved in the development of mammalian external genitals |
| title_full | A complex regulatory landscape involved in the development of mammalian external genitals |
| title_fullStr | A complex regulatory landscape involved in the development of mammalian external genitals |
| title_full_unstemmed | A complex regulatory landscape involved in the development of mammalian external genitals |
| title_short | A complex regulatory landscape involved in the development of mammalian external genitals |
| title_sort | complex regulatory landscape involved in the development of mammalian external genitals |
| topic | hox clusters TAD CTCF chromatin loop extrusion enhancers |
| url | https://elifesciences.org/articles/52962 |
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