Upregulation of BAK by butyrate in the colon is associated with increased Sp3 binding.
Butyrate is a key bioactive product of dietary fibre fermentation thought to play a key role in cancer prevention. One contributory mechanism in this role is the regulation of apoptosis by butyrate. As butyrate shows low levels of toxicity, the mechanisms by which it triggers or regulates apoptosis are of great interest. We and others have shown that the proapoptotic protein BAK is upregulated by butyrate. We show here that this observation is conserved across multiple cell lines, that it occurs in all cells in a population and is at the transcriptional level. We have used a promoter-reporter construct to identify the regulatory regions of the BAK promoter and found that much of the transcriptional activity occurs via a single Sp1/Sp3 binding site. We have shown that both Sp1 and Sp3 bind, but upon butyrate treatment Sp1 binding decreases in favour of Sp3 binding. We speculate that this may be an acetylation-mediated event.
Chirakkal
H
H
Human Nutrition Unit, Division of Clinical Sciences North, University of Sheffield, Northern General Hospital, Sheffield, UK.
Leech
S H
SH
Brookes
K E
KE
Prais
A L
AL
Waby
J S
JS
Corfe
B M
BM
D017209:Apoptosis / Q000502:physiology*; D015153:Blotting, Western; D020148:Butyric Acid / Q000378:metabolism*; D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D003106:Colon / Q000378:metabolism*; D004043:Dietary Fiber / Q000378:metabolism; D005434:Flow Cytometry; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D011401:Promoter Regions, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016329:Sp1 Transcription Factor / Q000378:metabolism; D051705:Sp3 Transcription Factor / Q000378:metabolism*; D015854:Up-Regulation; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000235:genetics / Q000378:metabolism*
C494772:BAK1 protein, human; D004043:Dietary Fiber; C497121:SP3 protein, human; D016329:Sp1 Transcription Factor; D050998:bcl-2 Homologous Antagonist-Killer Protein; D020148:Butyric Acid; D051705:Sp3 Transcription Factor