tailieunhanh - Báo cáo khoa học: How mammalian transcriptional repressors work Gerald Thiel, Michael Lietz1 and Mathias Hohl Department of Medical Biochemistry and Molecular

Research on the regulation of transcription in mammals initially focused on the mechanism of transcriptional acti-vation and positive control of gene regulation. In contrast, transcriptional repression and negative control of gene transcription was viewed rather as part of the prokaryotic book of biology . However, results obtained in recent years have shown convincingly that transcriptional repression mediated by repressor proteins is a common regulatory mechanism in mammals and may play a key role in many biological processes. . | Eur. J. Biochem. 271 2855-2862 2004 FEBS 2004 doi REVIEW ARTICLE How mammalian transcriptional repressors work Gerald Thiel Michael Lietz1 and Mathias Hohl Department of Medical Biochemistry and Molecular Biology University of the Saarland Medical Center Homburg Germany Research on the regulation of transcription in mammals initially focused on the mechanism of transcriptional activation and positive control of gene regulation. In contrast transcriptional repression and negative control of gene transcription was viewed rather as part of the prokaryotic book of biology . However results obtained in recent years have shown convincingly that transcriptional repression mediated by repressor proteins is a common regulatory mechanism in mammals and may play a key role in many biological processes. In particular the fact that human diseases such as Rett and ICF syndromes as well as some human forms of cancer are connected with the activities of human repressor proteins indicates that transcriptional repression and gene silencing is essential for maintenance of the cellular integrity of a multicellular organism. The wide range of diseases caused by aberration in transcriptional repression sheds light on the importance of understanding how mammalian transcriptional repressor proteins work. Keywords heterochromatin histone deacetylation MeCP2 REST retinoblastoma. Introduction Transcriptional repressor proteins such as the lac and tryptophan repressors were first discovered in prokaryotes. The DNA-tethered form of the repressor turns genes off by blocking RNA polymerase binding to the promoter or its movement along the DNA. Thus competition between a gene-specific repressor protein and RNA polymerase is the most common form of transcriptional regulation in Escherichia coli. In contrast many eukaryotic transcriptional activator proteins have been characterized in the last two decades suggesting that positive regulation via activator proteins is