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TET2 catalyzes active DNA demethylation of the Sry promoter and enhances its expression
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TET2 catalyzes active DNA demethylation of the Sry promoter and enhances its expression
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Journal Article
TET2 catalyzes active DNA demethylation of the Sry promoter and enhances its expression
2019
Overview
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.
Tet
2-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.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 45/23
/ 5-Methylcytosine - analogs & derivatives
/ 5-Methylcytosine - metabolism
/ 631/136
/ 64/60
/ Animals
/ DNA
/ DNA-Binding Proteins - genetics
/ DNA-Binding Proteins - metabolism
/ Female
/ Gene Expression Regulation, Developmental
/ Humanities and Social Sciences
/ Male
/ Proto-Oncogene Proteins - genetics
/ Proto-Oncogene Proteins - metabolism
/ Science
/ Sex-Determining Region Y Protein - genetics
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