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TET2 catalyzes active DNA demethylation of the Sry promoter and enhances its expression
- Source :
- Scientific Reports, Vol 9, Iss 1, Pp 1-11 (2019), Scientific Reports
- Publication Year :
- 2019
- Publisher :
- Nature Publishing Group, 2019.
-
Abstract
- SRY is the master regulator of male sex determination in eutherian mammals. In mice, Sry expression is transcriptionally and epigenetically controlled in a developmental stage-specific manner. The Sry promoter undergoes demethylation in embryonic gonadal somatic cells at the sex-determining period. However, its molecular mechanism and in vivo significance remain unclear. Here, we report that the Sry promoter is actively demethylated during gonadal development, and TET2 plays a fundamental role in Sry demethylation. Tet2-deficient mice showed absence of 5-hydroxymethylcytosine in the Sry promoter. Furthermore, Tet2 deficiency diminished Sry expression, indicating that TET2-mediated DNA demethylation regulates Sry expression positively. We previously showed that the deficiency of the H3K9 demethylase Jmjd1a compromises Sry expression and induces male-to-female sex reversal. Tet2 deficiency enhanced the sex reversal phenotype of Jmjd1a-deficient mice. Thus, TET2-mediated active DNA demethylation and JMJD1A-mediated H3K9 demethylation contribute synergistically to sex determination.
- Subjects :
- 0301 basic medicine
Male
Somatic cell
health care facilities, manpower, and services
Male sex determination
lcsh:Medicine
Mice, Transgenic
Biology
Steroidogenic Factor 1
Article
Dioxygenases
03 medical and health sciences
0302 clinical medicine
Proto-Oncogene Proteins
Developmental biology
parasitic diseases
Animals
Gonads
Promoter Regions, Genetic
lcsh:Science
Demethylation
Mice, Inbred ICR
Multidisciplinary
DNA methylation
lcsh:R
Gene Expression Regulation, Developmental
social sciences
Sex reversal
Sex Determination Processes
Phenotype
Sex-Determining Region Y Protein
Cell biology
DNA Demethylation
DNA-Binding Proteins
Mice, Inbred C57BL
030104 developmental biology
DNA demethylation
Testis determining factor
biology.protein
5-Methylcytosine
Demethylase
population characteristics
Female
lcsh:Q
030217 neurology & neurosurgery
geographic locations
Subjects
Details
- Language :
- English
- ISSN :
- 20452322
- Volume :
- 9
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Scientific Reports
- Accession number :
- edsair.doi.dedup.....b7f1bcea77d9e2635af2230e85921cc3