First Author | Gentile C | Year | 2019 |
Journal | Dev Cell | Volume | 50 |
Issue | 2 | Pages | 184-196.e4 |
PubMed ID | 31204170 | Mgi Jnum | J:284152 |
Mgi Id | MGI:6389763 | Doi | 10.1016/j.devcel.2019.05.021 |
Citation | Gentile C, et al. (2019) PRC2-Associated Chromatin Contacts in the Developing Limb Reveal a Possible Mechanism for the Atypical Role of PRC2 in HoxA Gene Expression. Dev Cell 50(2):184-196.e4 |
abstractText | 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. |