Histone Deacetylase 3-Progesterone Receptor Cooperation Regulates Progesterone Responsiveness in the Uterus.
5 affiliations
- 1Department of Obstetrics, Gynecology and Women's Health University of Missouri Columbia Missouri USA.
- 2Center For Reproductive Medicine and Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School Nanjing University Nanjing China.
- 3Department of Obstetrics and Gynecology Duke University Durham North Carolina USA.
- 4Department of Obstetrics and Gynecology Wake Forest Baptist Health Winston-Salem North Carolina USA.
- 5Department of Biomedical Laboratory Science Yonsei University Mirae Campus Wonju Republic of Korea.
Abstract
Endometriosis affects a substantial proportion of women of reproductive age, with 30%-50% affected by infertility. A defining pathological feature is progesterone resistance resulting from impaired progesterone receptor (PGR) signaling, yet the underlying mechanisms remain incompletely understood. Here, we define conserved shared target genes of histone deacetylase 3 (HDAC3) and PGR in the mouse uterus using integrated transcriptomic and cistromic analyses, supported by uterine-specific Hdac3 and Pgr knockout mice. Co-immunoprecipitation and proximity ligation assays indicate that HDAC3 associates with PGR, with reciprocal attenuation of their expression in Hdac3- and Pgr-deficient uteri. Multiplex immunofluorescence demonstrates colocalization of HDAC3 and PGR in endometrial epithelial and stromal cells. HDAC3 and PGR expression levels show a positive correlation in stromal cells in both controls and infertile women with endometriosis, whereas this correlation in epithelial cells is selectively preserved in a subset of infertile cases. Chromatin profiling demonstrates extensive co-occupancy of HDAC3 and PGR at regulatory regions associated with progesterone-responsive genes. Together, these findings support a model in which HDAC3 functions as a coregulator of PGR-dependent transcription in the uterus and indicate that HDAC3-PGR cooperation is a key determinant of endometrial receptivity. This work provides mechanistic insight into progesterone resistance underlying endometriosis-associated infertility.
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BibTeX
@article{yun2026histone,
title = {{Histone Deacetylase 3-Progesterone Receptor Cooperation Regulates Progesterone Responsiveness in the Uterus.}},
author = {Sohyeon Yun and Rong Li and Soo Lim Kim and Loan Thi Kim Nguyen and Shamsun Nahar and Keun Cheon Kim and DaHye Kang and Eunhee M Jeong and Lisa Brennaman and Mistie P Mills and Steven L Young and Bruce A Lessey and Tae Hoon Kim and Jung-Yoon Yoo and Jae-Wook Jeong},
journal = {MedComm},
year = {2026},
month = nov,
doi = {10.1002/mco2.71122},
url = {https://europepmc.org/article/MED/42996627},
note = {CC BY},
}
RIS
TY - JOUR
TI - Histone Deacetylase 3-Progesterone Receptor Cooperation Regulates Progesterone Responsiveness in the Uterus.
AU - Sohyeon Yun
AU - Rong Li
AU - Soo Lim Kim
AU - Loan Thi Kim Nguyen
AU - Shamsun Nahar
AU - Keun Cheon Kim
AU - DaHye Kang
AU - Eunhee M Jeong
AU - Lisa Brennaman
AU - Mistie P Mills
AU - Steven L Young
AU - Bruce A Lessey
AU - Tae Hoon Kim
AU - Jung-Yoon Yoo
AU - Jae-Wook Jeong
PY - 2026
DA - 2026/11/05
JO - MedComm
DO - 10.1002/mco2.71122
UR - https://europepmc.org/article/MED/42996627
AB - Endometriosis affects a substantial proportion of women of reproductive age, with 30%-50% affected by infertility. A defining pathological feature is progesterone resistance resulting from impaired progesterone receptor (PGR) signaling, yet the underlying mechanisms remain incompletely understood. Here, we define conserved shared target genes of histone deacetylase 3 (HDAC3) and PGR in the mouse uterus using integrated transcriptomic and cistromic analyses, supported by uterine-specific Hdac3 and Pgr knockout mice. Co-immunoprecipitation and proximity ligation assays indicate that HDAC3 associates with PGR, with reciprocal attenuation of their expression in Hdac3- and Pgr-deficient uteri. Multiplex immunofluorescence demonstrates colocalization of HDAC3 and PGR in endometrial epithelial and stromal cells. HDAC3 and PGR expression levels show a positive correlation in stromal cells in both controls and infertile women with endometriosis, whereas this correlation in epithelial cells is selectively preserved in a subset of infertile cases. Chromatin profiling demonstrates extensive co-occupancy of HDAC3 and PGR at regulatory regions associated with progesterone-responsive genes. Together, these findings support a model in which HDAC3 functions as a coregulator of PGR-dependent transcription in the uterus and indicate that HDAC3-PGR cooperation is a key determinant of endometrial receptivity. This work provides mechanistic insight into progesterone resistance underlying endometriosis-associated infertility.
SN - 2688-2663
ER -