Prolactin and its downstream transcription factor STAT5 are cornerstones of mammary alveolar development during pregnancy. They control the establishment of the alveolar progenitor pool and subsequent proliferation and differentiation of alveolar luminal cells, which culminates in the production of milk. STAT5 therefore controls distinct temporally- and context-dependent genetic programs. During puberty STAT5 controls the establishment of the progenitor pool, during the early phase of pregnancy it activates cell proliferation and, as pregnancy progresses, its role in promoting cell differentiation becomes prominent. Although these programs exhibit significant temporal overlap it can be hypothesized that STAT5 in cooperation with other transcription factors activates distinct genetic programs to achieve its different goals in the formation of the mammary gland.
Ongoing research focuses on three venues.
- Identification of STAT5-activated genetic programs throughout pregnancy
- Role of chromatin modifications in alveolar development
- Synergy of Nuclear factor 1 (NF1) and STAT5 in alveolar differentiatio
To explore these questions we use a set of experimental approaches. These include
- mouse genetics to delete relevant genes involved in chromatin modeling as well as NF1 genes
- ChIP-seq analyses to identify context-dependent binding of STAT5 and NF1 to chromatin
- ChIP-seq analyses to explore the changing chromatin landscape as alveolar cells progress through their developmental journey
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