GATA4 binding to the Sox9 enhancer mXYSRa/Enh13 is critical for testis differentiation in mouse
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 func...
Saved in:
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-01-01
|
| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-025-07504-2 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1823861747869548544 |
|---|---|
| author | Yuya Ogawa Iku Tsuchiya Shogo Yanai Takashi Baba Ken-Ichirou Morohashi Takehiko Sasaki Junko Sasaki Miho Terao Atsumi Tsuji-Hosokawa Shuji Takada |
| author_facet | Yuya Ogawa Iku Tsuchiya Shogo Yanai Takashi Baba Ken-Ichirou Morohashi Takehiko Sasaki Junko Sasaki Miho Terao Atsumi Tsuji-Hosokawa Shuji Takada |
| author_sort | Yuya Ogawa |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-a5afc51d1dde473299cbed672c0c0339 |
| institution | Kabale University |
| issn | 2399-3642 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj-art-a5afc51d1dde473299cbed672c0c03392025-02-09T12:50:47ZengNature PortfolioCommunications Biology2399-36422025-01-018111210.1038/s42003-025-07504-2GATA4 binding to the Sox9 enhancer mXYSRa/Enh13 is critical for testis differentiation in mouseYuya Ogawa0Iku Tsuchiya1Shogo Yanai2Takashi Baba3Ken-Ichirou Morohashi4Takehiko Sasaki5Junko Sasaki6Miho Terao7Atsumi Tsuji-Hosokawa8Shuji Takada9Department of Systems BioMedicine, National Research Institute for Child Health and DevelopmentDepartment of Systems BioMedicine, National Research Institute for Child Health and DevelopmentDepartment of Biochemical Pathophysiology/Lipid Biology, Medical Research Laboratory, Institute of Integrated Research, Institute of Science TokyoDepartment of Systems Life Sciences, Graduate School of Systems Life Sciences, Kyushu UniversityDepartment of Internal Medicine, Kurume University School of MedicineDepartment of Biochemical Pathophysiology/Lipid Biology, Medical Research Laboratory, Institute of Integrated Research, Institute of Science TokyoDepartment of Biochemical Pathophysiology/Lipid Biology, Medical Research Laboratory, Institute of Integrated Research, Institute of Science TokyoDepartment of Systems BioMedicine, National Research Institute for Child Health and DevelopmentDepartment of Systems BioMedicine, National Research Institute for Child Health and DevelopmentDepartment of Systems BioMedicine, National Research Institute for Child Health and DevelopmentAbstract 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.https://doi.org/10.1038/s42003-025-07504-2 |
| spellingShingle | Yuya Ogawa Iku Tsuchiya Shogo Yanai Takashi Baba Ken-Ichirou Morohashi Takehiko Sasaki Junko Sasaki Miho Terao Atsumi Tsuji-Hosokawa Shuji Takada GATA4 binding to the Sox9 enhancer mXYSRa/Enh13 is critical for testis differentiation in mouse Communications Biology |
| title | GATA4 binding to the Sox9 enhancer mXYSRa/Enh13 is critical for testis differentiation in mouse |
| title_full | GATA4 binding to the Sox9 enhancer mXYSRa/Enh13 is critical for testis differentiation in mouse |
| title_fullStr | GATA4 binding to the Sox9 enhancer mXYSRa/Enh13 is critical for testis differentiation in mouse |
| title_full_unstemmed | GATA4 binding to the Sox9 enhancer mXYSRa/Enh13 is critical for testis differentiation in mouse |
| title_short | GATA4 binding to the Sox9 enhancer mXYSRa/Enh13 is critical for testis differentiation in mouse |
| title_sort | gata4 binding to the sox9 enhancer mxysra enh13 is critical for testis differentiation in mouse |
| url | https://doi.org/10.1038/s42003-025-07504-2 |
| work_keys_str_mv | AT yuyaogawa gata4bindingtothesox9enhancermxysraenh13iscriticalfortestisdifferentiationinmouse AT ikutsuchiya gata4bindingtothesox9enhancermxysraenh13iscriticalfortestisdifferentiationinmouse AT shogoyanai gata4bindingtothesox9enhancermxysraenh13iscriticalfortestisdifferentiationinmouse AT takashibaba gata4bindingtothesox9enhancermxysraenh13iscriticalfortestisdifferentiationinmouse AT kenichiroumorohashi gata4bindingtothesox9enhancermxysraenh13iscriticalfortestisdifferentiationinmouse AT takehikosasaki gata4bindingtothesox9enhancermxysraenh13iscriticalfortestisdifferentiationinmouse AT junkosasaki gata4bindingtothesox9enhancermxysraenh13iscriticalfortestisdifferentiationinmouse AT mihoterao gata4bindingtothesox9enhancermxysraenh13iscriticalfortestisdifferentiationinmouse AT atsumitsujihosokawa gata4bindingtothesox9enhancermxysraenh13iscriticalfortestisdifferentiationinmouse AT shujitakada gata4bindingtothesox9enhancermxysraenh13iscriticalfortestisdifferentiationinmouse |