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

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Abstract
Development of murine proximal colon follows a complex pattern of morphological and functional differentiation. Molecular mechanisms and factors responsible for colonspecific gene expression remain to be established. In an attempt to identify some of these factors, we examined the expression of the α, β, and δ isoforms of the CCAAT/enhancer binding protein (C/EBP) transcription factor gene family during murine colon development. Whereas C/EBPα mRNA levels are reduced during the third post-natal week, C/EBPα 42 and 30 kD proteins levels decrease between post-natal days 8 and 21. C/EBPβ mRNA levels increase between post-natal days 4 and 8 and remain constant subsequently, in contrast to a decrease in C/EBPβ protein levels between post-natal days 11 and 15. C/EBPδ mRNA levels increase gradually while C/EBPδ 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/EBPα expression to differentiated surface epithelial cells during crypt formation. C/EBPβ is predominantly nuclear with some cytoplasmic staining at all developmental stages. C/EBPβ and δ 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.