Ovarian ERβ cistrome and transcriptome reveal chromatin interaction with LRH-1

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Birgersson, MadeleineKTH,Science for Life Laboratory, SciLifeLab,Proteinvetenskap,Karolinska Inst, Dept Biosci & Nutr, S-14183 Huddinge, Sweden. (author)

Ovarian ERβ cistrome and transcriptome reveal chromatin interaction with LRH-1

Article/chapterEnglish2023

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Springer Nature,2023
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LIBRIS-ID:oai:DiVA.org:kth-341540
https://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-341540URI
https://doi.org/10.1186/s12915-023-01773-1DOI
http://kipublications.ki.se/Default.aspx?queryparsed=id:154395841URI

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Language:English
Summary in:English

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QC 20231222
Background: Estrogen receptor beta (ERβ, Esr2) plays a pivotal role in folliculogenesis and ovulation, yet its exact mechanism of action is mainly uncharacterized.Results: We here performed ERβ ChIP-sequencing of mouse ovaries followed by complementary RNA-sequencing of wild-type and ERβ knockout ovaries. By integrating the ERβ cistrome and transcriptome, we identified its direct target genes and enriched biological functions in the ovary. This demonstrated its strong impact on genes regulating organism development, cell migration, lipid metabolism, response to hypoxia, and response to estrogen. Cell-type deconvolution analysis of the bulk RNA-seq data revealed a decrease in luteal cells and an increased proportion of theca cells and a specific type of cumulus cells upon ERβ loss. Moreover, we identified a significant overlap with the gene regulatory network of liver receptor homolog 1 (LRH-1, Nr5a2) and showed that ERβ and LRH-1 extensively bound to the same chromatin locations in granulosa cells. Using ChIP-reChIP, we corroborated simultaneous ERβ and LRH-1 co-binding at the ERβ-repressed gene Greb1 but not at the ERβ-upregulated genes Cyp11a1 and Fkbp5. Transactivation assay experimentation further showed that ERβ and LRH-1 can inhibit their respective transcriptional activity at classical response elements.Conclusions: By characterizing the genome-wide endogenous ERβ chromatin binding, gene regulations, and extensive crosstalk between ERβ and LRH-1, along with experimental corroborations, our data offer genome-wide mechanistic underpinnings of ovarian physiology and fertility.

Subject headings and genre

MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Cell- och molekylärbiologi hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Cell and Molecular Biology hsv//eng
ChIP-seq
ER beta
Esr2
LRH-1
Nr5a2
Ovary
RNA-seq

Added entries (persons, corporate bodies, meetings, titles ...)

Indukuri, RajithaKTH,Cellulär och klinisk proteomik,Science for Life Laboratory, SciLifeLab(Swepub:kth)u1h2gbg8 (author)
Lindquist, LinnéaKarolinska Institutet,KTH,Cellulär och klinisk proteomik,Science for Life Laboratory, SciLifeLab,Karolinska Inst, Dept Biosci & Nutr, S-14183 Huddinge, Sweden.(Swepub:kth)u14f1ler (author)
Stepanauskaite, LinaKTH,Cellulär och klinisk proteomik,Science for Life Laboratory, SciLifeLab,Karolinska Inst, Dept Biosci & Nutr, S-14183 Huddinge, Sweden.(Swepub:kth)u1xd7zej (author)
Luo, QingKarolinska Institutet (author)
Deng, QiaolinKarolinska Inst, Dept Physiol & Pharmacol, S-14183 Huddinge, Sweden. (author)
Archer, AmenaKTH,Cellulär och klinisk proteomik,Science for Life Laboratory, SciLifeLab,Karolinska Inst, Dept Biosci & Nutr, S-14183 Huddinge, Sweden.(Swepub:kth)u131bapq (author)
Williams, Cecilia,Professor,1969-Karolinska Institutet,KTH,Science for Life Laboratory, SciLifeLab,Cellulär och klinisk proteomik,Karolinska Inst, Dept Biosci & Nutr, S-14183 Huddinge, Sweden.(Swepub:kth)u1ygqmuy (author)
KTHScience for Life Laboratory, SciLifeLab (creator_code:org_t)

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In:BMC Biology: Springer Nature21:11741-7007

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