X chromosome dosage and presence of SRY shape sex-specific differences in DNA methylation at an autosomal region in human cells

Autores de IIS La Fe
Participantes ajenos a IIS La Fe
- Ho, B
- Greenlaw, K
- Al Tuwaijri, A
- Moussette, S
- Giorgio, E
- Brusco, A
- Ferrero, GB
- Linhares, ND
- Valadares, ER
- Svartman, M
- Kalscheuer, VM
- Criado, GR
- Laprise, C
- Greenwood, CMT
- Naumova, AK
Grupos
Abstract
Background: Sexual dimorphism in DNA methylation levels is a recurrent epigenetic feature in different human cell types and has been implicated in predisposition to disease, such as psychiatric and autoimmune disorders. To elucidate the genetic origins of sex-specific DNA methylation, we examined DNA methylation levels in fibroblast cell lines and blood cells from individuals with different combinations of sex chromosome complements and sex phenotypes focusing on a single autosomal region-the differentially methylated region (DMR) in the promoter of the zona pellucida binding protein 2 (ZPBP2) as a reporter. Results: Our data show that the presence of the sex determining region Y (SRY) was associated with lower methylation levels, whereas higher X chromosome dosage in the absence of SRY led to an increase in DNA methylation levels at the ZPBP2 DMR. We mapped the X-linked modifier of DNA methylation to the long arm of chromosome X (Xq13-q21) and tested the impact of mutations in the ATRX and RLIM genes, located in this region, on methylation levels. Neither ATRX nor RLIM mutations influenced ZPBP2 methylation in female carriers. Conclusions: We conclude that sex-specific methylation differences at the autosomal locus result from interaction between a Y-linked factor SRY and at least one X-linked factor that acts in a dose-dependent manner.
Datos de la publicación
- ISSN/ISSNe:
- 2042-6410, 2042-6410
- Tipo:
- Article
- Páginas:
- 10-10
- Factor de Impacto:
- 1,347 SCImago ℠
- Cuartil:
- Q1 SCImago ℠
Biology of Sex Differences BIOMED CENTRAL LTD
Citas Recibidas en Web of Science: 15
Documentos
- No hay documentos
Filiaciones
Keywords
- DNA methylation; Sex; X chromosome; Y chromosome
Proyectos asociados
RED DE BIOBANCOS (BIOBANCOS)
RD09/0076/00021 . INSTITUTO DE SALUD CARLOS III; FUNDACIÓN PARA LA INVESTIGACIÓN DEL HOSPITAL UNIVERSITARIO LA FE DE LA COMUNIDAD VALENCIANA . 2010
COMPREHENSIVE, INTEGRATIVE AND GENOMIC APPROACH TO THE UNDERSTANDING AND TREATMENT OF CANCER AND LEUKEMIA.
Investigador Principal: MIGUEL ÁNGEL SANZ ALONSO
PIE13/00046 . INSTITUTO DE SALUD CARLOS III; FUNDACIÓN PARA LA INVESTIGACIÓN DEL HOSPITAL UNIVERSITARIO LA FE DE LA COMUNIDAD VALENCIANA . 2014
LA RUTA DE LA OXITOCINA EN LOS TRASTORNOS DEL ESPECTRO AUTISTA: IMPORTANCIA DE LAS VARIANTES GENÉTICAS CON RELEVANCIA FUNCIONAL.
Investigador Principal: CARMEN ORELLANA ALONSO
2014_0056_CRC_ORELLANA . 2014
ABORDAJE GENÓMICO PARA LA IDENTIFICACIÓN DE NUEVOS GENES Y MÓDULOS FUNCIONALES RESPONSABLES DE DISCAPACIDAD INTELECTUAL GRAVE.
Investigador Principal: FRANCISCO MARTÍNEZ CASTELLANO
PI14/00350 . INSTITUTO DE SALUD CARLOS III . 2015
Cita
Ho B,Greenlaw K,Al Tuwaijri A,Moussette S,Martinez F,Giorgio E,Brusco A,Ferrero GB,Linhares ND,Valadares ER,Svartman M,Kalscheuer VM,Criado GR,Laprise C,Greenwood CMT,Naumova AK. X chromosome dosage and presence of SRY shape sex-specific differences in DNA methylation at an autosomal region in human cells. Biol Sex Differ. 2018. 9. (1):p. 10-10. IF:3,188. (2).