CCAAT/enhancer binding protein isoforms expression in the colon of neonatal mice

Abstract

Development of murine proximal colon follows a complex pattern of morphological and functional differentiation. Molecular mechanisms and factors responsible for colon-specific gene expression remain to be established. In an attempt to identify some of these factors, we examined the expression of the alpha, beta, and delta isoforms of the CCAAT/enhancer binding protein (C/EBP) transcription factor gene family during murine colon development. Whereas C/EBP alpha mRNA levels are reduced during the third post-natal week, C/EBP alpha 42 and 30 kD proteins levels decrease between post-natal days 8 and 21. C/EBP beta mRNA levels increase between post-natal days 4 and 8 and remain constant subsequently, in contrast to a decrease in C/EBP beta protein levels between post-natal days 11 and 15. C/EBP delta mRNA levels increase gradually while C/EBP delta protein levels show variations during post-natal development. Changes in C/EBP DNA binding activity coincides with modifications 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 differentiated surface epithelial cells, as well as in various cells of the lamina propria and muscular layers. Thus, specific C/EBP isoforms are differentially regulated during murine colon post-natal development. Differential C/EBP isoforms pattern of expression suggests a role for these transcription factors in colon-specific gene expression during development.