Analysis of Drosophila p8 and p52 mutants reveals distinct roles for the maintenance of TFIIH stability and male germ cell differentiation.
Eukaryotic gene expression is activated by factors that interact within complex machinery to initiate transcription. An important component of this machinery is the DNA repair/transcription factor TFIIH. Mutations in TFIIH result in three human syndromes: xeroderma pigmentosum, Cockayne syndrome and trichothiodystrophy. Transcription and DNA repair defects have been linked to some clinical features of these syndromes. However, how mutations in TFIIH affect specific developmental programmes, allowing organisms to develop with particular phenotypes, is not well understood. Here, we show that mutations in the p52 and p8 subunits of TFIIH have a moderate effect on the gene expression programme in the Drosophila testis, causing germ cell differentiation arrest in meiosis, but no Polycomb enrichment at the promoter of the affected differentiation genes, supporting recent data that disagree with the current Polycomb-mediated repression model for regulating gene expression in the testis. Moreover, we found that TFIIH stability is not compromised in p8 subunit-depleted testes that show transcriptional defects, highlighting the role of p8 in transcription. Therefore, this study reveals how defects in TFIIH affect a specific cell differentiation programme and contributes to understanding the specific syndrome manifestations in TFIIH-afflicted patients.
Departamento de Genética del Desarrollo, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Av Universidad 2001, Cuernavaca Morelos 62250, Mexico.
Grisel
G
Cruz-Becerra
Departamento de Genética del Desarrollo, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Av Universidad 2001, Cuernavaca Morelos 62250, Mexico.
Mandy
M
Juárez
Departamento de Genética del Desarrollo, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Av Universidad 2001, Cuernavaca Morelos 62250, Mexico.
Viviana
V
Valadez-Graham
Departamento de Genética del Desarrollo, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Av Universidad 2001, Cuernavaca Morelos 62250, Mexico marioz@ibt.unam.mx.
Mario
0000-0002-8404-2173
M
Zurita
D000818:Animals; D002454:Cell Differentiation; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics; D004331:Drosophila melanogaster / Q000254:growth & development*; D020869:Gene Expression Profiling; D008297:Male; D009154:Mutation; D055550:Protein Stability; D013094:Spermatozoa / Q000166:cytology*; D013737:Testis / Q000166:cytology / Q000196:embryology; D051758:Transcription Factor TFIIH / Q000737:chemistry* / Q000235:genetics*; D014158:Transcription, Genetic
D029721:Drosophila Proteins; D051758:Transcription Factor TFIIH
Drosophila; TFIIH; cell differentiation; meiotic arrest; spermatogenesis; transcription