RRC ID 83165
著者 Ogawa Y, Tsuchiya I, Yanai S, Baba T, Morohashi KI, Sasaki T, Sasaki J, Terao M, Tsuji-Hosokawa A, Takada S.
タイトル GATA4 binding to the Sox9 enhancer mXYSRa/Enh13 is critical for testis differentiation in mouse.
ジャーナル Commun Biol
Abstract In mammals, SOX9/Sox9 expression in embryonic gonads is essential for male gonadal sex determination. Multiple enhancers of Sox9 have been identified, of which the mXYSRa/Enh13 enhancer plays a crucial role in mice. SOX9 and SRY binding sites within the enhancer have been identified as functional. Simultaneous deletion of both sites in mice resulted in male-to-female sex reversal. However, the existence of other critical functional sequences remains unclear. This study identified an additional functional sequence by generating mice with partial deletions in mXYSRa/Enh13. Two nucleotide substitutions within the sequence were sufficient for male-to-female sex reversal. In vivo binding assay by CUT&RUN revealed that GATA4 binds to the sequence. In vitro luciferase assay showed that GATA4 promotes the enhancer activity and the substitution of the sequence reduces the effect. Taken together, the functional sequence in mXYSRa/Enh13 is essential for testis differentiation and requires GATA4 binding.
巻・号 8(1)
ページ 81
公開日 2025-1-18
DOI 10.1038/s42003-025-07504-2
PII 10.1038/s42003-025-07504-2
PMID 39827212
PMC PMC11743149
MeSH Animals Binding Sites Cell Differentiation Enhancer Elements, Genetic* Female GATA4 Transcription Factor* / genetics GATA4 Transcription Factor* / metabolism Gene Expression Regulation, Developmental Male Mice Protein Binding SOX9 Transcription Factor* / genetics SOX9 Transcription Factor* / metabolism Sex Differentiation / genetics Testis* / embryology Testis* / growth & development Testis* / metabolism
IF 4.165
リソース情報
遺伝子材料 pcDNA3.1-Gata4 (RDB20787) pGL4.10-mXYSRa sub-HBBpro (RDB20788) gRNA_A (RDB20778) gRNA_B (RDB20779) gRNA_C (RDB20780) gRNA_D (RDB20781) gRNA_E (RDB20782) gRNA_G (RDB20783) gRNA_H (RDB20784) gRNA_I (RDB20785) gRNA_J (RDB20786)