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Transcription regulation: P53 Utilizes HDACs to Repress Transcription

Science's STKE  26 Oct 1999:
Vol. 1999, Issue 5, pp. tw2
DOI: 10.1126/stke.1999.5.tw2

The mechanism by which the tumor suppressor protein p53 inhibits the expression of certain target genes has not been clear. Murphy et al. now suggest that transcriptional repression by p53 involves recruitment of histone deacetylases (HDACs) to the genes repressed by p53. HDACs, which are known to have a role in gene repression by other transcription factors, was found in a complex with p53 in vivo. Furthermore, this interaction was mediated by mSin3a, a known corepressor. The authors suggest that when this protein complex is associated with the promotor of the p53 target gene Map4, the histones bound to the promoter become deacetylated and dissociate. Just how p53 is targeted to the promoters of target genes that are repressed has yet to be determined.

Murphy, M., Ahn, J., Walker, K.K., Hoffman, W.H., Evans, R.M., Levine, A.J., and George, D.L. (1999) Transcriptional repression by wild-type p53 histone deacetylases, mediated by interaction with mSin3a. Genes Dev. 13: 2490-2501. [Abstract] [Full Text]