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| Status |
Public on Aug 01, 2024 |
| Title |
Unexpected nuclear hormone receptor and chromatin dynamics regulate estrous cycle dependent gene expression [ATAC-seq] |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Hormone dependent uterine gene expression changes that occur during the estrous cycle suggest hormone receptor binding to chromatin may also be dynamic. Therefore, we employed a multi-faceted approach to examine in vivo dynamics of hormone receptor occupancy, chromatin accessibility and chromatin structure by combining RNA-seq, ATAC-seq, HiC-seq and ChIP-seq for estrogen receptor alpha (ERα) and progesterone receptor (PGR). Genome wide, there were extensive estrous cycle dependent changes in ERα and PGR binding as well as chromatin accessibility. There were 4,159 differentially expressed genes between estrus and diestrus. At transcription start sites, accessibility generally correlated with the directionality of gene expression and there was reduced PGR in estrus compared to diestrus but little change in ERα. There were 2,727 enhancers with dynamic accessibility near these genes and 77% of those correlated with directionality of gene expression changes. However, most enhancers were constitutively open (8,694). In both dynamic and constitutively open enhancers, ERα and PgR binding was coordinately lost from diestrus to estrus. Diestrus specific ERα binding and accessible regions were enriched for PGR, FOX, GATA and SOX binding motifs. In contrast, estrus specific ERα binding occurred at transcription factor deserts in relatively closed chromatin while estrus specific accessible regions were highly enriched for ATF, ELF and ELK motifs. Rapid Immunoprecipitation Mass spectrometry of Endogenous proteins (RIME) revealed many estrous cycle dependent partners of ERα (diestrus, 60; estrus, 24). PGR was found in complex with ERα during diestrus but not estrus supporting coordinated binding of both receptors during diestrus. Two of the cohesin complex proteins, SMC1A and SMC3, were found in complex with ERα during diestrus but not estrus; overlap of SMC1A with ERα confirmed this preferential interaction during diestrus. Additionally, HiC analysis showed more diestrus specific interactions than estrus (476 versus 263) suggesting the SMC1A/ ERα interactions have functional consequences on chromatin structure. Taken together, a complex series of interactions between hormone receptors, chromatin structure and accessibility orchestrate estrous cycle dependent changes in gene expression.
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| Overall design |
Uteri from intact, untreated CD-1 mice were collected at 2 months of age at diestrus (CoD) or estrus (CoE). RNA-seq, ATAC-seq, ER alpha ChIP-seq, PgR ChIP-seq, Hif2a ChIP-seq and HiC-seq were performed as well as RIME assay using ER alpha as the immunoprecipitating antibody.
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| Contributor(s) |
Jefferson W, Wang T, Williams C |
| Citation(s) |
39166489 |
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| Submission date |
Jun 02, 2023 |
| Last update date |
Oct 31, 2024 |
| Contact name |
Wendy Jefferson |
| E-mail(s) |
jeffers1@niehs.nih.gov
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| Organization name |
NIEHS
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| Street address |
111 TW alexander Drive
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| City |
RTP |
| State/province |
NC |
| ZIP/Postal code |
27709 |
| Country |
USA |
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| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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| Samples (2) |
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| This SubSeries is part of SuperSeries: |
| GSE234065 |
Unexpected nuclear hormone receptor and chromatin dynamics regulate estrous cycle dependent gene expression |
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| Relations |
| BioProject |
PRJNA979242 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE234051_RAW.tar |
162.4 Mb |
(http)(custom) |
TAR (of BW) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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