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Mol Cell Endocrinol. 2018 Jul 15;470:75-83. doi: 10.1016/j.mce.2017.09.033. Epub 2017 Sep 28.

Estrogen-induced transcription factor EGR1 regulates c-Kit transcription in the mouse uterus to maintain uterine receptivity for embryo implantation.

Author information

1
Department of Biomedical Science, CHA University, Seongnam, Republic of Korea.
2
Fertility Center of Gangnam Medical Center, CHA University, Seoul, Republic of Korea.
3
Department of Veterinary Medicine, Konkuk University, Seoul, Republic of Korea.
4
Department of Internal Medicine, Kangwon National University, Chuncheon, Kangwon, Republic of Korea. Electronic address: shhong@kangwon.ac.kr.
5
Department of Biomedical Science, CHA University, Seongnam, Republic of Korea. Electronic address: hssong@cha.ac.kr.

Abstract

Early growth response 1 (Egr1) is a key transcription factor that mediates the action of estrogen (E2) to establish uterine receptivity for embryo implantation. However, few direct target genes of EGR1 have been identified in the uterus. Here, we demonstrated that E2 induced EGR1-regulated transcription of c-Kit, which plays a crucial role in cell fate decisions. Spatiotemporal expression of c-Kit followed that of EGR1 in uteri of ovariectomized mice at various time points after E2 treatment. E2 activated ERK1/2 and p38 to induce EGR1, which then activated c-Kit expression in the uterus. EGR1 transfection produced rapid and transient induction of c-KIT in a time- and dose-dependent manner. Furthermore, luciferase assays to measure c-Kit promoter activity confirmed that a functional EGR1 binding site(s) (EBS) was located within -1 kb of the c-Kit promoter. Site-directed mutagenesis and chromatin immunoprecipitation-PCR for three putative EBS within -1 kb demonstrated that the EBS at -818/-805 was critical for EGR1-dependent c-Kit transcription. c-Kit expression was significantly increased in the uterus on day 4 and administration of Masitinib, a c-Kit inhibitor, effectively interfered with embryo implantation. Collectively, our results showed that estrogen induces transcription factor EGR1 to regulate c-Kit transcription for uterine receptivity for embryo implantation in the mouse uterus.

KEYWORDS:

EGR1; Embryo implantation; Estrogen; Transcription; Uterus; c-Kit

PMID:
28965972
DOI:
10.1016/j.mce.2017.09.033

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