GTMB 7 - Gene Therapy & Molecular Biology

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Suzuki et al: Regulation of the Sp/KLF-family of transcription factorsthrough cooperative interaction with chromatinremodelingfactors.The zinc finger transcription factors are the mostwidely evolved family of transcription factors ineukaryotes. Given that this biological diversification wascoupled with the evolution of nuclear structure ineukaryotes, it is conceivable that regulation of chromatinis a necessary process to further allow for efficient use andaccess of factors to the tightly packaged DNA geneticinformation. Important mechanisms of transcriptionalregulation in the context of chromatin have been shown asdiscussed in this review. The mechanism that the DBDmediates important regulation of the DNA-bindingtranscription factors through interaction and modificationwith chromatin factors can certainly be generalized toDNA-binding transcription factors other than thedescribed zinc finger factors. Selectivity may be foundbetween interaction of subsets for chromatin factors andDBD motifs. Furthermore, although only three types ofchromatin factors were described including modificationenzymes (e.g. acetyltransferase), ATP-independent (e.g.histone chaperones) and ATP-dependent (Swi/snf) factors,other chromatin factors are likely also to participate inregulatory interactions. Understanding the hierarchy andnetwork of regulation among DNA-binding transcriptionfactors and chromatin factors will likely play an importantrole in understanding the complexity of eukaryotictranscriptional regulation. As the Sp/KLF factors are a keyfamily important in mammalian biological processesranging from development, differentiation, to oncogenicprocesses, further studies aimed at understanding thetemporospatial regulation of chromatin centered onSp/KLF factors will surely advance our understanding ofeukaryotic transcriptional mechanisms of chromatinactivation in a biological context. Future gene therapyapproaches could use strategies of expressing suchactivator, modifier or factor genes individually or incomplexed form to facilitate regulation of therapeuticallyimportant genes at the physiologically relevant chromatinDNA level.AcknowledgementsThis study was supported by grants from the NewEnergy and Industrial Technology DevelopmentOrganization, Ministry of Health, Labour and Welfare,Ministry of Education, Culture, Sports, Science andTechnology, Japan Science and Technology Corporation,Sankyo Life Science Foundation, Takeda MedicalResearch Foundation, and the Applied EnzymeAssociation.ReferencesArmstrong SA, Barry DA, Leggett RW and Mueller CR (1997)Casein kinase II-mediated phosphorylation of the C terminusof Sp1 decreases its DNA binding activity. J Biol Chem 272,13489-3495.Bieker, JJ (2001) Krüppel-like factors: three fingers in manypies. 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