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 1alpha,25-dihydroxyvitamin D(3), were shown to attenuate transcription of the cyclin D1 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 D1 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 D1 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 D1 intron 3.
Maier
Sandra
S
Department of Medicine, Albert Einstein College of Medicine, Bronx, New York 10467, USA.
Daroqui
M Cecilia
MC
Scherer
Stefan
S
Roepcke
Stefan
S
Velcich
Anna
A
Shenoy
Shailesh M
SM
Singer
Robert H
RH
Augenlicht
Leonard H
LH
D000818:Animals; D001483:Base Sequence; D002087:Butyrates / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002762:Cholecalciferol / Q000494:pharmacology*; D003110:Colonic Neoplasms / Q000235:genetics*; D019938:Cyclin D1 / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007438:Introns / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D014158:Transcription, Genetic / Q000187:drug effects*
D002087:Butyrates; C530104:CCND1 protein, human; D019938:Cyclin D1; D002762:Cholecalciferol