title: Transcription-dependent dynamic supercoiling is a short-range genomic force.
abstract: Transcription has the capacity to mechanically modify DNA topology, DNA structure and nucleosome arrangement. Resulting from ongoing transcription, these modifications in turn may provide instant feedback to the transcription machinery. To substantiate the connection between transcription and DNA dynamics, we charted an ENCODE map of transcription-dependent dynamic supercoiling in human Burkitt's lymphoma cells by using psoralen photobinding to probe DNA topology in vivo. Dynamic supercoils spread ~1.5 kilobases upstream of the start sites of active genes. Low- and high-output promoters handled this torsional stress differently, as shown by using inhibitors of transcription and topoisomerases and by chromatin immunoprecipation of RNA polymerase and topoisomerases I and II. Whereas lower outputs are managed adequately by topoisomerase I, high-output promoters additionally require topoisomerase II. The genome-wide coupling between transcription and DNA topology emphasizes the importance of dynamic supercoiling for gene regulation.
authors: Laboratory of Pathology, National Cancer Institute, Bethesda, Maryland, USA.
authors: Fedor
authors: F
authors: Kouzine
authors: Ashutosh
authors: A
authors: Gupta
authors: Laura
authors: L
authors: Baranello
authors: Damian
authors: D
authors: Wojtowicz
authors: Khadija
authors: K
authors: Ben-Aissa
authors: Juhong
authors: J
authors: Liu
authors: Teresa M
authors: TM
authors: Przytycka
authors: David
authors: D
authors: Levens
mesh_terms: D002051:Burkitt Lymphoma / Q000235:genetics; D047369:Chromatin Immunoprecipitation; D003432:Cross-Linking Reagents; D004264:DNA Topoisomerases, Type I / Q000235:genetics / Q000378:metabolism; D004250:DNA Topoisomerases, Type II / Q000235:genetics / Q000378:metabolism; D004278:DNA, Superhelical / Q000737:chemistry*; D005363:Ficusin / Q000737:chemistry; D005786:Gene Expression Regulation; D006801:Humans; D011401:Promoter Regions, Genetic; D024363:Transcription Initiation Site; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
chemical_list: D003432:Cross-Linking Reagents; D004278:DNA, Superhelical; D004264:DNA Topoisomerases, Type I; C528909:TOP1 protein, human; D004250:DNA Topoisomerases, Type II; D005363:Ficusin