Chromatin topology defines estradiol-primed progesterone receptor and PAX2 binding in endometrial cancer cells.
ChIPseq
PAX2
cancer biology
cell biology
estrogen receptor
gene regulation
human
progesterone receptor
Journal
eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614
Informations de publication
Date de publication:
12 01 2022
12 01 2022
Historique:
received:
22
12
2020
accepted:
11
01
2022
pubmed:
13
1
2022
medline:
5
4
2022
entrez:
12
1
2022
Statut:
epublish
Résumé
Estrogen (E2) and Progesterone (Pg), via their specific receptors (ERalpha and PR), are major determinants in the development and progression of endometrial carcinomas, However, their precise mechanism of action and the role of other transcription factors involved are not entirely clear. Using Ishikawa endometrial cancer cells, we report that E2 treatment exposes a set of progestin-dependent PR binding sites which include both E2 and progestin target genes. ChIP-seq results from hormone-treated cells revealed a non-random distribution of PAX2 binding in the vicinity of these estrogen-promoted PR sites. Altered expression of hormone regulated genes in PAX2 knockdown cells suggests a role for PAX2 in fine-tuning ERalpha and PR interplay in transcriptional regulation. Analysis of long-range interactions by Hi-C coupled with ATAC-seq data showed that these regions, that we call 'progestin control regions' (PgCRs), exhibited an open chromatin state even before hormone exposure and were non-randomly associated with regulated genes. Nearly 20% of genes potentially influenced by PgCRs were found to be altered during progression of endometrial cancer. Our findings suggest that endometrial response to progestins in differentiated endometrial tumor cells results in part from binding of PR together with PAX2 to accessible chromatin regions. What maintains these regions open remains to be studied.
Identifiants
pubmed: 35018885
doi: 10.7554/eLife.66034
pii: 66034
pmc: PMC8887898
doi:
pii:
Substances chimiques
Chromatin
0
Estrogen Receptor alpha
0
PAX2 Transcription Factor
0
PAX2 protein, human
0
Receptors, Progesterone
0
Progesterone
4G7DS2Q64Y
Estradiol
4TI98Z838E
Banques de données
GEO
['GSE139398', 'GSE132713', 'GSE41466']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2022, La Greca et al.
Déclaration de conflit d'intérêts
AL, NB, FL, RJ, AN, JQ, JV, EV, GM, CF, IT, GV, GV, EF, MB, PS No competing interests declared
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