PRC2-Associated Chromatin Contacts in the Developing Limb Reveal a Possible Mechanism for the Atypical Role of PRC2 in HoxA Gene Expression
| Autor: | Marie Kmita, Claudia Gentile, Fanny Guerard-Millet, Soizik Berlivet, Josée Dostie, Denis Paquette, Alexandre Mayran, Emmanuel Bajon |
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| Rok vydání: | 2018 |
| Předmět: |
macromolecular substances
Biology General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Mice 0302 clinical medicine Gene silencing Animals Enhancer Hox gene Promoter Regions Genetic Molecular Biology 030304 developmental biology Regulation of gene expression Homeodomain Proteins 0303 health sciences Polycomb Repressive Complex 2 Cell Biology Chromatin Cell biology Enhancer Elements Genetic Gene Expression Regulation Lower Extremity Regulatory sequence biology.protein PRC1 PRC2 030217 neurology & neurosurgery Developmental Biology |
| Zdroj: | Developmental cell. 50(2) |
| ISSN: | 1878-1551 |
| Popis: | Preventing inappropriate gene expression in time and space is as fundamental as triggering the activation of tissue- or cell-type-specific factors at the correct developmental stage and in the correct cells. Here, we study the impact of Polycomb repressive complex 2 (PRC2) function on HoxA gene regulation. We analyze chromatin conformation of the HoxA cluster and its regulatory regions and show that in addition to the well-known role of PRC2 in silencing Hox genes via direct binding, its function is required for the changes in HoxA long-range interactions distinguishing proximal limbs from distal limbs. This effect stems from the differential PRC2 occupancy over the HoxA cluster and, at least in part, from the ability of PRC2-bound loci to engage in long-range contacts. Unexpectedly, PRC2 also impacts chromatin conformation in a way that promotes enhancer-promoter contacts required for proper HoxA expression, pointing to a dual role of PRC2 in gene regulation. |
| Databáze: | OpenAIRE |
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