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DOI10.1073/pnas.2024067118
Sexual fate of murine external genitalia development: Conserved transcriptional competency for male-biased genes in both sexes
Kajioka D.; Suzuki K.; Matsushita S.; Hino S.; Sato T.; Takada S.; Isono K.; Takeo T.; Kajimoto M.; Nakagata N.; Nakao M.; Suyama M.; DeFalco T.; Miyagawa S.; Yamada G.
发表日期2021
ISSN0027-8424
卷号118期号:23
英文摘要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. © 2021 National Academy of Sciences. All rights reserved.
英文关键词Androgen responsiveness; External genitalia; Histone modifications; Sex differentiation; Sp1
语种英语
scopus关键词androgen receptor; histone H3; transcription factor Sp1; androgen; androgen receptor; histone; Mafb protein, mouse; transcription factor; transcription factor MafB; 3' untranslated region; animal tissue; Article; controlled study; female; gender bias; gene; gene editing; gene expression; genetic conservation; genetic manipulation; genetic transcription; genital system; histone acetylation; MafB gene; male; nonhuman; regulatory mechanism; regulatory sequence; sequence analysis; sex differentiation; sexual development; acetylation; animal; C57BL mouse; CRISPR Cas system; gene expression regulation; Institute for Cancer Research mouse; knockout mouse; male genital system; metabolism; mouse; sex differentiation; Acetylation; Androgens; Animals; CRISPR-Cas Systems; Female; Gene Expression Regulation; Genitalia, Male; Histones; MafB Transcription Factor; Male; Mice; Mice, Inbred C57BL; Mice, Inbred ICR; Mice, Knockout; Receptors, Androgen; Sex Differentiation; Transcription Factors
来源期刊Proceedings of the National Academy of Sciences of the United States of America
文献类型期刊论文
条目标识符http://gcip.llas.ac.cn/handle/2XKMVOVA/251151
作者单位Department of Developmental Genetics, Institute of Advanced Medicine, Wakayama Medical University, Wakayama, 641-8509, Japan; Department of Medical Cell Biology, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, 860-0811, Japan; Division of Bioinformatics, Medical Institute of Bioregulation, Kyushu University, Fukuoka, 812-8582, Japan; Department of Systems BioMedicine, National Research Institute for Child Health and Development, Tokyo, 157-8535, Japan; Laboratory Animal Center, Wakayama Medical University, Wakayama, 641-8509, Japan; Division of Reproductive Engineering, Center for Animal Resources and Development, Institute of Resource Development and Analysis, Kumamoto University, Kumamoto, 860-0811, Japan; Division of Reproductive Biotechnology and Innovation, Institute of Resource Development and Analysis, Kumamoto University, Kumamoto, 860-0811, Japan; Division of Reproductive Sciences, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, United States; ...
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Kajioka D.,Suzuki K.,Matsushita S.,et al. Sexual fate of murine external genitalia development: Conserved transcriptional competency for male-biased genes in both sexes[J],2021,118(23).
APA Kajioka D..,Suzuki K..,Matsushita S..,Hino S..,Sato T..,...&Yamada G..(2021).Sexual fate of murine external genitalia development: Conserved transcriptional competency for male-biased genes in both sexes.Proceedings of the National Academy of Sciences of the United States of America,118(23).
MLA Kajioka D.,et al."Sexual fate of murine external genitalia development: Conserved transcriptional competency for male-biased genes in both sexes".Proceedings of the National Academy of Sciences of the United States of America 118.23(2021).
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