STAT5-Driven Enhancers Tightly Control Temporal Expression of Mammary-Specific Genes
- Authors
- Shin, Ha Youn; Hennighausen, Lothar; Yoo, Kyung Hyun
- Issue Date
- Mar-2019
- Publisher
- SPRINGER/PLENUM PUBLISHERS
- Keywords
- STAT5; Enhancer; Mammary-specific gene expression
- Citation
- JOURNAL OF MAMMARY GLAND BIOLOGY AND NEOPLASIA, v.24, no.1, pp 61 - 71
- Pages
- 11
- Journal Title
- JOURNAL OF MAMMARY GLAND BIOLOGY AND NEOPLASIA
- Volume
- 24
- Number
- 1
- Start Page
- 61
- End Page
- 71
- URI
- https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/3756
- DOI
- 10.1007/s10911-018-9418-y
- ISSN
- 1083-3021
1573-7039
- Abstract
- The de novo formation of milk-secreting mammary epithelium during pregnancy is regulated by prolactin through activation of the transcription factor STAT5, which stimulates the expression of several hundred mammary-specific genes. In addition to its key role in activating gene expression in mammary tissue, STAT5, which is ubiquitously expressed in most cell types, implements T cell-specific programs controlled by interleukins. However, the mechanisms by which STAT5 controls cell-specific genetic programs activated by distinct cytokines remain relatively unknown. Integration of data from genome-wide surveys of chromatin markers and transcription factor binding at regulatory elements may shed light on the mechanisms that drive cell-specific programs. Here, we have illustrated how STAT5 controls cell-specific gene expression through its concentration and an auto-regulatory enhancer supporting its high levels in mammary tissue. The unique genomic features of STAT5-driven enhancers or super-enhancers that regulate mammary-specific genes and their dynamic remodeling in response to pregnancy hormone levels are described. We have further provided biological evidence supporting the in vivo function of a STAT5-driven super-enhancer with the aid of CRISPR/Cas9 genome editing. Finally, we discuss how the functions of mammary-specific super-enhancers are confined by the zinc finger protein, CTCF, to allow exclusive activation of mammary-specific genes without affecting common neighboring genes. This review comprehensively summarizes the molecular pathways underlying differential control of cell-specific gene sets by STAT5 and provides novel insights into STAT5-dependent mammary physiology.
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