title: Transcription factories, chromatin loops, and the dysregulation of gene expression in malignancy.
abstract: Pathologists recognize and classify cancers according to nuclear morphology, but there remains little scientific explanation of why malignant nuclei possess their characteristic features, or how those features are related to dysregulated function. This essay will discuss a basic structure-function axis that connects one central architectural motif in the nucleus-the chromatin loop-to the vital nuclear function of transcription. The loop is attached to a "transcription factory" through components of the transcription machinery (either polymerases or transcriptional activators/repressors), and the position of a gene within a loop determines how often that gene is transcribed. Then, dysregulated transcription is tightly coupled to alterations in structure, and vice versa. We also speculate on how the experimental approaches being used to analyze loops and factories might be applied to study the problems of tumour initiation and progression.
authors.affiliation: Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford, OX1 3RE, UK.
authors.forename: Binwei
authors.initials: B
authors.lastname: Deng
authors.forename: Svitlana
authors.initials: S
authors.lastname: Melnik
authors.forename: Peter R
authors.initials: PR
authors.lastname: Cook
mesh_terms: D000818:Animals; D002843:Chromatin / Q000737:chemistry*; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008954:Models, Biological; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology; D009690:Nucleic Acid Conformation; D011401:Promoter Regions, Genetic / Q000502:physiology; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology; D014158:Transcription, Genetic / Q000235:genetics / Q000502:physiology*
chemical_list: D002843:Chromatin; D014157:Transcription Factors; D004259:DNA-Directed DNA Polymerase