How mammalian transcriptional repressors work

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Abstract
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.