Sustained activation of STAT5 is essential for chromatin remodeling and maintenance of mammary-specifi c function

Ren Xu, Celeste M. Nelson, John L. Muschler, Mandana Veiseh, Barbara K. Vonderhaar, Mina J. Bissell

Research output: Contribution to journalArticle

79 Scopus citations

Abstract

Epithelial cells, once dissociated and placed in twodimensional (2D) cultures, rapidly lose tissue-specifi c functions. We showed previously that in addition to prolactin, signaling by laminin-111 was necessary to restore functional differentiation of mammary epithelia. Here, we elucidate two additional aspects of laminin-111 action. We show that in 2D cultures, the prolactin receptor is basolaterally localized and physically segregated from its apically placed ligand. Detachment of the cells exposes the receptor to ligation by prolactin leading to signal transducers and activators of transcription protein 5 (STAT5) activation, but only transiently and not suffi ciently for induction of milk protein expression. We show that laminin-111 reorganizes mammary cells into polarized acini, allowing both the exposure of the prolactin receptor and sustained activation of STAT5. The use of constitutively active STAT5 constructs showed that the latter is necessary and suffi cient for chromatin reorganization and β-casein transcription. These results underscore the crucial role of continuous laminin signaling and polarized tissue architecture in maintenance of transcription factor activation, chromatin organization, and tissue-specific gene expression.

Original languageEnglish (US)
Pages (from-to)57-66
Number of pages10
JournalJournal of Cell Biology
Volume184
Issue number1
DOIs
StatePublished - Jan 12 2009

ASJC Scopus subject areas

  • Cell Biology

Fingerprint Dive into the research topics of 'Sustained activation of STAT5 is essential for chromatin remodeling and maintenance of mammary-specifi c function'. Together they form a unique fingerprint.

  • Cite this