TY - JOUR
T1 - C/EBPβ LIP and c-Jun synergize to regulate expression of the murine progesterone receptor
AU - Wang, Weizhong
AU - Do, Han Ngoc
AU - Aupperlee, Mark D.
AU - Durairaj, Srinivasan
AU - Flynn, Emily E.
AU - Miksicek, Richard J.
AU - Haslam, Sandra Z.
AU - Schwartz, Richard C.
N1 - Publisher Copyright:
© 2018 The Authors
PY - 2018/12/5
Y1 - 2018/12/5
N2 - CCAAT/enhancer binding protein β (C/EBPβ) is required for murine mammary ductal morphogenesis and alveologenesis. Progesterone is critical for proliferation and alveologenesis in adult mammary glands, and there is a similar requirement for progesterone receptor isoform B (PRB) in alveologenesis. We examined C/EBPβ regulation of PR expression. All three C/EBPβ isoforms, including typically inhibitory LIP, transactivated the PR promoter. LIP, particularly, strongly synergized with c-Jun to drive PR transcription. Endogenous C/EBPβ and c-Jun stimulated a PR promoter-reporter and these two factors showed promoter occupancy on the endogenous PR gene. Additionally, LIP overexpression elevated endogenous PR protein expression. In pregnancy, both PRB and the relative abundance of LIP among C/EBPβ isoforms increase. Consistent with a role in PRB expression, in vivo C/EBPβ and PR isoform A expression showed mutually exclusive localization in mammary epithelium, while C/EBPβ and PRB largely co-localized. We suggest a critical role for C/EBPβ particularly LIP, in PRB expression.
AB - CCAAT/enhancer binding protein β (C/EBPβ) is required for murine mammary ductal morphogenesis and alveologenesis. Progesterone is critical for proliferation and alveologenesis in adult mammary glands, and there is a similar requirement for progesterone receptor isoform B (PRB) in alveologenesis. We examined C/EBPβ regulation of PR expression. All three C/EBPβ isoforms, including typically inhibitory LIP, transactivated the PR promoter. LIP, particularly, strongly synergized with c-Jun to drive PR transcription. Endogenous C/EBPβ and c-Jun stimulated a PR promoter-reporter and these two factors showed promoter occupancy on the endogenous PR gene. Additionally, LIP overexpression elevated endogenous PR protein expression. In pregnancy, both PRB and the relative abundance of LIP among C/EBPβ isoforms increase. Consistent with a role in PRB expression, in vivo C/EBPβ and PR isoform A expression showed mutually exclusive localization in mammary epithelium, while C/EBPβ and PRB largely co-localized. We suggest a critical role for C/EBPβ particularly LIP, in PRB expression.
KW - c-Jun
KW - C/EBPβLIP
KW - Progesterone receptor
KW - Synergistic regulation
KW - Transcription
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UR - http://www.scopus.com/inward/citedby.url?scp=85047925354&partnerID=8YFLogxK
U2 - 10.1016/j.mce.2018.06.001
DO - 10.1016/j.mce.2018.06.001
M3 - Article
C2 - 29870755
AN - SCOPUS:85047925354
SN - 0303-7207
VL - 477
SP - 57
EP - 69
JO - Molecular and Cellular Endocrinology
JF - Molecular and Cellular Endocrinology
ER -
