transcription factor and that ﬁne tuning of p21 transcription is ensured by subtle variations in the ability of nuclear repres- sors such as NFI to interact with its corresponding target site in the p21 promoter. Our results are consistent with those published by other groups who demonstrated that while basal transcription of p21 is regulated by both Sp1 and Sp3 in cultured primary mouse keratinocytes, only Sp3 contributes to the calcium-induced p21 promoter activity (67). The identiﬁcation of each of the nuclear proteins yielding the new protected sites identiﬁed in this study as well as the precise regulatory function they play will be required to assess the precise mechanisms that modulate p21-dependent regulation of cell cycle progression. We must now look upon NFI as a new and central player in the molecular mechanisms regulating p21 expression during cell cycle pro- gression. The relationship between NFI and other transcrip- tion factors such as p53, Sp1, Sp3 and E2F1 that also bind the p21 promoter will be of a particular interest and should prove to be particularly fascinating regarding p21 gene regulation. ACKNOWLEDGEMENTS The authors are grateful to Drs R. Stephen Lloyd and Tim R. O’Connor for supplying T4 endonuclease V and photolyase, respectively and to Dr R.M. Gronostajski for the NFI expression plasmids. This work was supported by grants from the NSERC (grant OGP0138624) to S.L.G. and the National Cancer Institute of Canada (NCIC) (with funds from the Canadian Cancer Society and the Terry Fox Run) to R.D. F.V. holds a Doctoral Research Award from the Canadian Institute for Health Research (CIHR). R.D. and S.L.G. are research scholars (Senior and National levels, respectively) from the ‘Fonds de la Recherche en Sante´ du Que´bec (FRSQ). R.D. holds a Canada Research Chair in ‘Genetics, Mutagenesis and Cancer’. 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