title: Evolutionary conservation of TFIIH subunits: implications for the use of zebrafish as a model to study TFIIH function and regulation.
abstract: Transcriptional factor IIH (TFIIH) is involved in cell cycle regulation, nucleotide excision repair, and gene transcription. Mutations in three of its subunits, XPB, XPD, and TTDA, lead to human recessive genetic disorders such as trichothiodystrophy and xeroderma pigmentosum, the latter of which is sometimes associated with Cockayne's syndrome. In the present study, we investigate the sequence conservation of TFIIH subunits among several teleost fish species and compare their characteristics and putative regulation by transcription factors to those of human and zebrafish. We report the following findings: (i) comparisons among protein sequences revealed a high sequence identity for each TFIIH subunit analysed; (ii) among transcription factors identified as putative regulators, OCT1 and AP1 have the highest binding-site frequencies in the promoters of TFIIH genes, and (iii) TFIIH genes have alternatively spliced isoforms. Finally, we compared the protein primary structure in human and zebrafish of XPD and XPB - two important ATP-dependent helicases that catalyse the unwinding of the DNA duplex at promoters during transcription - highlighting the conservation of domain regions such as the helicase domains. Our study suggests that zebrafish, a widely used model for many human diseases, could also act as an important model to study the function of TFIIH complex in repair and transcription regulation in humans.
authors.affiliation: Department of Biomedical Sciences and Medicine, University of Algarve, Faro, Portugal; Centre of Marine Sciences (CCMAR), University of Algarve, Faro, Portugal.
authors.forename: I A L
authors.initials: IA
authors.lastname: Silva
authors.affiliation: Centre of Marine Sciences (CCMAR), University of Algarve, Faro, Portugal.
authors.forename: C J
authors.initials: CJ
authors.lastname: Cox
authors.affiliation: Centre of Marine Sciences (CCMAR), University of Algarve, Faro, Portugal.
authors.forename: R B
authors.initials: RB
authors.lastname: Leite
authors.affiliation: Department of Biomedical Sciences and Medicine, University of Algarve, Faro, Portugal; Centre of Marine Sciences (CCMAR), University of Algarve, Faro, Portugal.
authors.forename: M L
authors.initials: ML
authors.lastname: Cancela
authors.affiliation: Centre of Marine Sciences (CCMAR), University of Algarve, Faro, Portugal. Electronic address: nconcei@ualg.pt.
authors.forename: N
authors.initials: N
authors.lastname: Conceição
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002874:Chromosome Mapping; D017124:Conserved Sequence; D019143:Evolution, Molecular; D005399:Fishes / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D050811:Octamer Transcription Factor-1 / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011487:Protein Conformation; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism; D051758:Transcription Factor TFIIH / Q000737:chemistry / Q000502:physiology*; D051759:Xeroderma Pigmentosum Group D Protein / Q000737:chemistry / Q000235:genetics; D015027:Zebrafish / Q000235:genetics; D029961:Zebrafish Proteins / Q000235:genetics
chemical_list: D050811:Octamer Transcription Factor-1; D018808:Transcription Factor AP-1; D029961:Zebrafish Proteins; D051758:Transcription Factor TFIIH; D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human
keywords: Transcription regulation; Transcriptional factor IIH (TFIIH); Xeroderma pigmentosum B (XPB); Xeroderma pigmentosum D (XPD); Zebrafish