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Letter

Tissue-specific expression and regulation of sexually dimorphic genes in mice

¹ Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, California 90095, USA; ² Rosetta Inpharmatics, LLC, a Wholly Owned Subsidiary of Merck & Co. Inc., Seattle, Washington 98109, USA; ³ Department of Human Genetics, University of California, Los Angeles, California 90095, USA; ⁴ Department of Statistics, College of Letters and Science, University of California, Los Angeles, California 90095, USA; ⁵ Department of Physiological Science, and Laboratory of Neuroendocrinology of the Brain Research Institute, University of California, Los Angeles, California 90095, USA; ⁶ Department of Pathology and Laboratory Medicine, University of California, Los Angeles, California 90095, USA

We report a comprehensive analysis of gene expression differences between sexes in multiple somatic tissues of 334 mice derived from an intercross between inbred mouse strains C57BL/6J and C3H/HeJ. The analysis of a large number of individuals provided the power to detect relatively small differences in expression between sexes, and the use of an intercross allowed analysis of the genetic control of sexually dimorphic gene expression. Microarray analysis of 23,574 transcripts revealed that the extent of sexual dimorphism in gene expression was much greater than previously recognized. Thus, thousands of genes showed sexual dimorphism in liver, adipose, and muscle, and hundreds of genes were sexually dimorphic in brain. These genes exhibited highly tissue-specific patterns of expression and were enriched for distinct pathways represented in the Gene Ontology database. They also showed evidence of chromosomal enrichment, not only on the sex chromosomes, but also on several autosomes. Genetic analyses provided evidence of the global regulation of subsets of the sexually dimorphic genes, as the transcript levels of a large number of these genes were controlled by several expression quantitative trait loci (eQTL) hotspots that exhibited tissue-specific control. Moreover, many tissue-specific transcription factor binding sites were found to be enriched in the sexually dimorphic genes.

E-mail jlusis{at}mednet.ucla.edu; fax (310) 794-7345.

Article published online before print. Article and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.5217506

[Supplemental material is available online at www.genome.org. The microarray data from this study have been deposited to GEO under accession nos. GSE2814, GSE3086, GSE3087, and GSE3088.]

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