Regulation by the extracellular matrix (ECM) of prolactin‐induced αs1‐casein gene expression in rabbit primary mammary cells: Role of STAT5, C/EBP, and chromatin structure

Medientyp: E-Artikel

Titel: Regulation by the extracellular matrix (ECM) of prolactin‐induced αs1‐casein gene expression in rabbit primary mammary cells: Role of STAT5, C/EBP, and chromatin structure

Beteiligte: Jolivet, Geneviève; Pantano, Thaïs; Houdebine, Louis Marie

Erschienen: Wiley, 2005

Sprache: Englisch

DOI: 10.1002/jcb.20397

ISSN: 0730-2312; 1097-4644

Entstehung:

Anmerkungen:

Beschreibung: AbstractThe aim of the present study was to understand how the extracellular matrix (ECM) regulates at the gene level the prolactin (Prl)‐induced signal transducer and activator of transcription 5 (STAT5)‐dependent expression of the αs1‐casein gene in mammary epithelial cells. CCAAT enhancer binding proteins (C/EBPs) are assumed regulators of β‐casein gene expression. Rabbit primary mammary cells express αs1‐casein gene when cultured on collagen and not on plastic. Similar C/EBPβ, C/EBPδ, STAT5, and Prl‐activated STAT5 were found under all culture conditions. Thus the ECM does not act through C/EBPs or STAT5. This was confirmed by transfections of rabbit primary mammary cells by a construct sensitive to ovine prolactin (oPrl) and ECM (6i TK luc) encompassing STAT5 and C/EBP binding sites. The mutation of C/EBPs binding sites showed that these sites were not mandatory for Prl‐induced expression of the construct. Interestingly, chromatin immunoprecipitation by the anti‐acetylhistone H4 antibody (ChIP) showed that the ECM (and not Prl) maintained a high amount of histone H4 acetylation upstream of the αs1‐casein gene especially at the level of a distal Prl‐ and ECM‐ sensitive enhancer. Alpha6 integrin (a membrane receptor of laminin, the principal active component of the mammary ECM) was found at the surface of cells cultured on collagen but not on plastic. In cells cultured on collagen in the presence of anti‐α6 integrin antibody, Prl‐induced transcription of the endogenous αs1‐casein gene was significantly reduced, without modifying C/EBPs and STAT5. Besides, histone H4 acetylation was reduced. Thus, we propose that the ECM regulates rabbit αs1‐casein protein expression by local modification of chromatin structure, independently of STAT5 and C/EBPs. Copyright © 2005 Wiley‐Liss, Inc.

Nur in Feld suchen:

Zuletzt gesuchte Begriffe: