CCAAT ENHANCER BINDING-PROTEIN ISOFORMS EXPRESSION IN THE COLON OF NEONATAL MICE/

Development of murine proximal colon follows a complex pattern of morp hological and functional differentiation. Molecular mechanisms and fac tors responsible for colon-specific gene expression remain to be estab lished, In an attempt to identify some of these factors, we examined t he expression of the alpha, beta, and delta isoforms of the CCAAT/enha ncer binding protein (C/EBP) transcription factor gene family during m urine colon development. Whereas C/EBP alpha mRNA levels are reduced d uring the third post-natal week, C/EBP alpha 42 and 30 kD proteins lev els decrease between post-natal days 8 and 21, C/EBP beta mRNA levels increase between post-natal days 4 and 8 and remain constant subsequen tly, in contrast to a decrease in C/EBP alpha protein levels between p ost-natal days 11 and 15. C/EBP delta mRNA levels increase gradually w hile C/EBP delta protein levels show variations during post-natal deve lopment, Changes in C/EBP DNA binding activity coincides with modifica tions in C/EBP isoforms expression, By indirect immunofluorescence, we show restriction of C/EBP alpha expression to differentiated surface epithelial cells during crypt formation, C/EBP alpha is predominantly nuclear with some cytoplasmic staining at all developmental stages, C/ EBP beta and delta are both predominantly nuclear in crypt and differe ntiated surface epithelial cells, as well as in various cells of the l amina propria and muscular layers, Thus, specific C/EBP isoforms are d ifferentially regulated during murine colon post-natal development, Di fferential C/EBP isoforms pattern of expression suggests a role for th ese transcription factors in colon-specific gene expression during dev elopment. (C) 1995 Wiley-Liss, Inc.