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Sex‐dependent regulation of cytochrome P450 family members Cyp1a1, Cyp2e1, and Cyp7b1 by methylation of DNA
Author(s) -
Penaloza Carlos G.,
Estevez Brian,
Han Dinah M.,
Norouzi Melissa,
Lockshin Richard A.,
Zakeri Zahra
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.13-233320
Subject(s) - dna methylation , biology , methylation , gene , gene expression , promoter , epigenetics , cytochrome p450 , regulation of gene expression , sexual differentiation , genetics , microbiology and biotechnology , endocrinology , metabolism
Sexual differences are only partially attributable to hormones. Cultured male or female cells, even from embryos before sexual differentiation, differ in gene expression and sensitivity to toxins, and these differences persist in isolated primary cells. Male and female cells from Swiss Webster CWF mice manifest sex‐distinct patterns of DNA methylation for X‐ist and for cytochrome P450 (CYP; family members 1a1, 2e1m, and 7b1. Dnmt3l is differentially expressed but not differentially methylated, and Gapdh is neither differentially methylated nor expressed. CYP family genes differ in expression in whole tissue homogenates and cell cultures, with female Cyp expression 2‐ to 355‐fold higher and Dnmt3l 12‐ to 32‐fold higher in males. DNA methylation in the promoters of these genes is sex dimorphic; reducing methylation differences reduces to 1‐ to 6‐fold differences in the expression of these genes. Stress or estradiol alters both methylation and gene expression. We conclude that different methylation patterns partially explain the sex‐based differences in expression of CYP family members and X‐ist, which potentially leads to inborn differences between males and females and their different responses to chronic and acute changes. Sex‐differential methylation may have medical effects.—Penaloza, C.G., Estevez, B., Han, D.M., Norouzi, M., Lockshin, R.A., Zakeri, Z. Sex‐dependent regulation of cytochrome P450 family members Cyp1a1, Cyp2e1, and Cyp7b1 by methylation of DNA. FASEB J. 28, 966–977 (2014). www.fasebj.org