Cell-type specific concentration regulation of the basal transcription factor TFIIH in XPBy/y mice model

Cancer Cell International

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[1] 0000 0001 2150 7757, grid.7849.2, Institut NeuroMyoGène (INMG), CNRS, UMR 5310, INSERM U1217, Faculté de Médecine, Université Claude Bernard Lyon 1, 8 Avenue Rockefeller, 69008, LYON, France;0000 0001 2171 2558, grid.5842.b, Pathology Department, Saint-Louis Hospital, Université de Paris, 1 Avenue Claude Vellefaux, 75010, Paris, France;000000040459992X, grid.5645.2, Department of Genetics, Erasmus MC, Dr Molewaterplein 50, 3015 GE, Rotterdam, The Netherlands;

关键词: TFIIH;    Transcription;    Proliferation;   

DOI  :  10.1186/s12935-019-0945-4

来源: publisher

【 摘 要 】

BackgroundThe basal transcription/repair factor TFIIH is a ten sub-unit complex essential for RNA polymerase II (RNAP2) transcription initiation and DNA repair. In both these processes TFIIH acts as a DNA helix opener, required for promoter escape of RNAP2 in transcription initiation, and to set the stage for strand incision within the nucleotide excision repair (NER) pathway.MethodsWe used a knock-in mouse model that we generated and that endogenously expresses a fluorescent version of XPB (XPB-YFP). Using different microscopy, cellular biology and biochemistry approaches we quantified the steady state levels of this protein in different cells, and cells imbedded in tissues.ResultsHere we demonstrate, via confocal imaging of ex vivo tissues and cells derived from this mouse model, that TFIIH steady state levels are tightly regulated at the single cell level, thus keeping nuclear TFIIH concentrations remarkably constant in a cell type dependent manner. Moreover, we show that individual cellular TFIIH levels are proportional to the speed of mRNA production, hence to a cell’s transcriptional activity, which we can correlate to proliferation status. Importantly, cancer tissue presents a higher TFIIH than normal healthy tissues.ConclusionThis study shows that TFIIH cellular concentration can be used as a bona-fide quantitative marker of transcriptional activity and cellular proliferation.

【 授权许可】

CC BY