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Sexually dimorphic gene expression emerges with embryonic genome activation and is dynamic throughout development

Title: Sexually dimorphic gene expression emerges with embryonic genome activation and is dynamic throughout development
Author(s): Lowe, R
Gemma, C
Rakyan, VK
Holland, ML
Item Type: Journal Article
Abstract: As sex determines mammalian development, understanding the nature and developmental dynamics of the sexually dimorphic transcriptome is important. To explore this, we generated 76 genome-wide RNA-seq profiles from mouse eight-cell embryos, late gestation and adult livers, together with 4 ground-state pluripotent embryonic (ES) cell lines from which we generated both RNA-seq and multiple ChIP-seq profiles. We complemented this with previously published data to yield 5 snap-shots of pre-implantation development, late-gestation placenta and somatic tissue and multiple adult tissues for integrative analysis.We define a high-confidence sex-dimorphic signature of 69 genes in eight-cell embryos. Sex-chromosome-linked components of this signature are largely conserved throughout pre-implantation development and in ES cells, whilst the autosomal component is more dynamic. Sex-biased gene expression is reflected by enrichment for activating and repressive histone modifications. The eight-cell signature is largely non-overlapping with that defined from fetal liver, neither was it correlated with adult liver or other tissues analysed. The number of sex-dimorphic genes increases throughout development. We identified many more dimorphic genes in adult compared to fetal liver. However, approximately two thirds of the dimorphic genes identified in fetal liver were also dimorphic in adult liver. Sex-biased expression differences unique to adult liver were enriched for growth hormone-responsiveness. Sexually dimorphic gene expression in pre-implantation development is driven by sex-chromosome based transcription, whilst later development is characterised by sex dimorphic autosomal transcription.This systematic study identifies three distinct phases of sex dimorphism throughout mouse development, and has significant implications for understanding the developmental origins of sex-specific phenotypes and disease in mammals.
Publication Date: 14-Apr-2015
Date of Acceptance: 30-Mar-2015
URI: http://hdl.handle.net/10044/1/34421
DOI: http://dx.doi.org/10.1186/s12864-015-1506-4
ISSN: 1471-2164
Publisher: BioMed Central
Journal / Book Title: BMC Genomics
Volume: 16
Copyright Statement: © Lowe et al. 2015. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.
Keywords: Animals
Embryo, Mammalian
Embryonic Development
Female
Gene Expression Regulation, Developmental
Genome
Male
Mice
Pregnancy
Sex Characteristics
Sex Chromosomes
Transcriptome
Sex Chromosomes
Animals
Mice
Gene Expression Regulation, Developmental
Embryonic Development
Pregnancy
Sex Characteristics
Genome
Female
Male
Embryo, Mammalian
Transcriptome
Bioinformatics
06 Biological Sciences
11 Medical And Health Sciences
08 Information And Computing Sciences
Publication Status: Published
Article Number: 295
Appears in Collections:Division of Surgery
Division of Cancer
Faculty of Medicine



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