Butyrate and Vitamin D3 Induce Transcriptional Attenuation at the Cyclin D1 Locus in Colonic Carcinoma Cells

In stimulating maturation of colonic carcinoma cells, the short chain fatty acid butyrate, and 1 alpha,25-dihydroxyvitamin D-3, were shown to attenuate transcription of the cyclin DI gene, giving rise to truncated transcripts of this locus. Moreover, a sequence which is highly conserved in the human, mouse, rat, and dog genome was found in the 4 kb long intron 3 of the human cyclin DI gene, and is capable of forming a hairpin structure similar to that of microRNA precursors. The expression of this sequence is also decreased by the attenuation. Thus, the transcriptional attenuation at the cyclin DI locus not only down-regulates the expression of this key gene in mucosal cell maturation and tumorigenesis, but may also abrogate the generation of a molecule that encompasses this conserved sequence in cyclin DI intron 3.