| First Author | Jefferson WN | Year | 2024 |
| Journal | Nucleic Acids Res | Volume | 52 |
| Issue | 18 | Pages | 10897-10917 |
| PubMed ID | 39166489 | Mgi Jnum | J:358098 |
| Mgi Id | MGI:7779723 | Doi | 10.1093/nar/gkae714 |
| Citation | Jefferson WN, et al. (2024) Unexpected nuclear hormone receptor and chromatin dynamics regulate estrous cycle dependent gene expression. Nucleic Acids Res 52(18):10897-10917 |
| abstractText | Chromatin changes in response to estrogen and progesterone are well established in cultured cells, but how they control gene expression under physiological conditions is largely unknown. To address this question, we examined in vivo estrous cycle dynamics of mouse uterus hormone receptor occupancy, chromatin accessibility and chromatin structure by combining RNA-seq, ATAC-seq, HiC-seq and ChIP-seq. Two estrous cycle stages were chosen for these analyses, diestrus (highest estrogen) and estrus (highest progesterone). Unexpectedly, rather than alternating with each other, estrogen receptor alpha (ERalpha) and progesterone receptor (PGR) were co-bound during diestrus and lost during estrus. Motif analysis of open chromatin followed by hypoxia inducible factor 2A (HIF2A) ChIP-seq and conditional uterine deletion of this transcription factor revealed a novel role for HIF2A in regulating diestrus gene expression patterns that were independent of either ERalpha or PGR binding. Proteins in complex with ERalpha included PGR and cohesin, only during diestrus. Combined with HiC-seq analyses, we demonstrate that complex chromatin architecture changes including enhancer switching are coordinated with ERalpha and PGR co-binding during diestrus and non-hormone receptor transcription factors such as HIF2A during estrus to regulate most differential gene expression across the estrous cycle. |
