Canonical Wnt/β-catenin activity and differential epigenetic marks direct sexually dimorphic regulation of Irx3 and Irx5 in developing mouse gonads.

Autor:	Koth ML; Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin - Madison, Madison, WI 53706, USA., Garcia-Moreno SA; Department of Obstetrics and Gynecology, Northwestern University, Chicago, IL 60611, USA., Novak A; Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin - Madison, Madison, WI 53706, USA., Holthusen KA; Department of Comparative Biosciences, College of Veterinary Medicine, University of Illinois, Urbana, IL 61802, USA., Kothandapani A; Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin - Madison, Madison, WI 53706, USA., Jiang K; Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin - Madison, Madison, WI 53706, USA., Taketo MM; Department of Pharmacology, Kyoto University Graduate School of Medicine, Kyoto 606-8501, Japan., Nicol B; Reproductive and Developmental Biology Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA., Yao HH; Reproductive and Developmental Biology Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA., Futtner CR; Department of Obstetrics and Gynecology, Northwestern University, Chicago, IL 60611, USA., Maatouk DM; Department of Obstetrics and Gynecology, Northwestern University, Chicago, IL 60611, USA., Jorgensen JS; Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin - Madison, Madison, WI 53706, USA joan.jorgensen@wisc.edu.
Jazyk:	angličtina
Zdroj:	Development (Cambridge, England) [Development] 2020 Mar 30; Vol. 147 (6). Date of Electronic Publication: 2020 Mar 30.
DOI:	10.1242/dev.183814
Abstrakt:	Members of the Iroquois B (IrxB) homeodomain cluster genes, specifically Irx3 and Irx5 , are crucial for heart, limb and bone development. Recently, we reported their importance for oocyte and follicle survival within the developing ovary. Irx3 and Irx5 expression begins after sex determination in the ovary but remains absent in the fetal testis. Mutually antagonistic molecular signals ensure ovary versus testis differentiation with canonical Wnt/β-catenin signals paramount for promoting the ovary pathway. Notably, few direct downstream targets have been identified. We report that Wnt/β-catenin signaling directly stimulates Irx3 and Irx5 transcription in the developing ovary. Using in silico analysis of ATAC- and ChIP-Seq databases in conjunction with mouse gonad explant transfection assays, we identified TCF/LEF-binding sequences within two distal enhancers of the IrxB locus that promote β-catenin-responsive ovary expression. Meanwhile, Irx3 and Irx5 transcription is suppressed within the developing testis by the presence of H3K27me3 on these same sites. Thus, we resolved sexually dimorphic regulation of Irx3 and Irx5 via epigenetic and β-catenin transcriptional control where their ovarian presence promotes oocyte and follicle survival vital for future ovarian health. Competing Interests: Competing interestsThe authors declare no competing or financial interests. (© 2020. Published by The Company of Biologists Ltd.)
Databáze:	MEDLINE
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