Horm Mol Biol Clin Investig. 2012 Mar 01;10(1):201-205. doi: 10.1515/hmbci-2012-0004.

The chromatin landscape of the casein gene locus.

Hormone molecular biology and clinical investigation

Monique Rijnkels, Elena Kabotyanski, Amy Shore, Jeffrey M Rosen

PMID: 23914258 PMCID: PMC3729923 DOI: 10.1515/hmbci-2012-0004

Abstract

For several decades, the regulation of casein gene expression by the lactogenic hormones, prolactin and glucocorticoids, has provided an excellent model system in which to study how steroid and peptide hormones regulate gene expression. Early studies of casein gene regulation defined conserved sequence elements in the 5' flanking region of these genes, including one of which was identified as a γ-interferon activation sequence (GAS). Although this site was thought to interact with a mammary gland-specific factor, purification and cloning of this factor by Bernd Groner and his colleagues revealed it was instead a new member of the signal transducers and activators of transcription family, Stat5, which was expressed in many tissues. The exquisite tissue-specific expression of the casein genes was subsequently shown to depend not on a single transcription factor but on composite response elements that interacted with a number of ubiquitous transcription factors in response to the combinatorial effects of peptide and steroid hormone signaling. More recent studies have defined cooperative effects of prolactin and glucocorticoids as well as antagonistic effects of progesterone on the chromatin structure of both the casein gene proximal promoter region as well as a distal enhancer. Local chromatin modifications as well as long-range interactions facilitated by DNA looping are required for the hormonal regulation of

Keywords: Stat5; casein genes; chromatin conformation; glucocorticoids; prolactin

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Publication Types

• Journal Article

Grant support

• R01 CA016303/CA/NCI NIH HHS/United States
• R37 CA016303/CA/NCI NIH HHS/United States