Thiel Gerald, Lietz Michael, Hohl Mathias
Department of Medical Biochemistry and Molecular Biology, University of the Saarland Medical Center, Homburg, Germany.
Eur J Biochem. 2004 Jul;271(14):2855-62. doi: 10.1111/j.1432-1033.2004.04174.x.
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.
哺乳动物转录调控的研究最初聚焦于转录激活机制以及基因调控的“正调控”。相比之下,基因转录的转录抑制和“负调控”则更多地被视为“原核生物生物学手册”的一部分。然而,近年来获得的结果令人信服地表明,阻遏蛋白介导的转录抑制是哺乳动物中一种常见的调控机制,并且可能在许多生物学过程中起关键作用。特别是,诸如瑞特综合征和ICF综合征以及某些人类癌症等人类疾病与人类阻遏蛋白的活性相关这一事实表明,转录抑制和基因沉默对于维持多细胞生物体的细胞完整性至关重要。由转录抑制异常引起的广泛疾病揭示了理解哺乳动物转录阻遏蛋白如何发挥作用的重要性。