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Identification of Cux2 binding sites in female and male mouse liver

ABSTRACT: Growth hormone (GH)-regulated transcription factors, notably STAT5 and BCL6, play a major role in regulating genes showing sex differences in expression in mouse liver, primarily through their effects in male liver, where male-biased genes are up regulated and many female-biased genes are actively repressed. Here we investigate whether complementary mechanisms, involving up regulation of female-biased genes and down regulation of male-biased genes occur in female liver. To address this question, we identified genes regulated by Cux2, a highly female-specific transcription factor that is repressed in male liver and is induced by the female plasma GH pattern in female liver. ChIP-seq analysis identified Cux2 binding sites in female liver only, where they are enriched at sites of male-biased DNase hypersensitivity and at genomic regions showing male-enriched STAT5 binding. Cux2 binding sites were enriched at genes repressed by adenoviral-Cux2, but not at genes induced by adenoviral-Cux2 (see GSE35897), indicating a direct binding mechanism in Cux2 repression but not in Cux2-dependent gene induction. (Published in: TL Conforto et al 2012, Mol Cell Biol. 2012, 32:4611-4627. PubMed PMID: 22966202; PMCID: PMC3486175) Mouse livers were excised from individual male and female. Sonicated, cross-linked liver nuclear chromatin was then used to identify Cux2 binding sites by ChIP-Seq using antibody specific to Cux2, amino acids 356 to 415


ORGANISM(S): Mus musculus  

SUBMITTER: Tara L Conforto   David J Waxman  Yijing Zhang  David J. Waxman 

PROVIDER: E-GEOD-35985 | ArrayExpress | 2012-09-10



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Impact of CUX2 on the female mouse liver transcriptome: activation of female-biased genes and repression of male-biased genes.

Conforto Tara L TL   Zhang Yijing Y   Sherman Jennifer J   Waxman David J DJ  

Molecular and cellular biology 20120910 22

The growth hormone-regulated transcription factors STAT5 and BCL6 coordinately regulate sex differences in mouse liver, primarily through effects in male liver, where male-biased genes are upregulated and many female-biased genes are actively repressed. Here we investigated whether CUX2, a highly female-specific liver transcription factor, contributes to an analogous regulatory network in female liver. Adenoviral overexpression of CUX2 in male liver induced 36% of female-biased genes and repress  ...[more]

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