Sexual fate of murine external genitalia development: Conserved transcriptional competency for male-biased genes in both sexes

Daiki Kajioka, Kentaro Suzuki, Shoko Matsushita, Shinjiro Hino, Tetsuya Sato, Shuji Takada, Kyoichi Isono, Toru Takeo, Mizuki Kajimoto, Naomi Nakagata, Mitsuyoshi Nakao, Mikita Suyama, Tony DeFalco, Shinichi Miyagawa, Gen Yamada

研究成果: Contribution to journalArticle査読

抄録

Testicular androgen is a master endocrine factor in the establishment of external genital sex differences. The degree of androgenic exposure during development is well known to determine the fate of external genitalia on a spectrum of female- to male-specific phenotypes. However, the mechanisms of androgenic regulation underlying sex differentiation are poorly defined. Here, we show that the genomic environment for the expression of male-biased genes is conserved to acquire androgen responsiveness in both sexes. Histone H3 at lysine 27 acetylation (H3K27ac) and H3K4 monomethylation (H3K4me1) are enriched at the enhancer of male-biased genes in an androgen-independent manner. Specificity protein 1 (Sp1), acting as a collaborative transcription factor of androgen receptor, regulates H3K27ac enrichment to establish conserved transcriptional competency for male-biased genes in both sexes. Genetic manipulation of MafB, a key regulator of male-specific differentiation, and Sp1 regulatory MafB enhancer elements disrupts male-type urethral differentiation. Altogether, these findings demonstrate conservation of androgen responsiveness in both sexes, providing insights into the regulatory mechanisms underlying sexual fate during external genitalia development.

本文言語英語
論文番号e2024067118
ジャーナルProceedings of the National Academy of Sciences of the United States of America
118
23
DOI
出版ステータス出版済み - 6 8 2021

All Science Journal Classification (ASJC) codes

  • 一般

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