title: Requirement for SNAPC1 in transcriptional responsiveness to diverse extracellular signals.
abstract: Initiation of transcription of RNA polymerase II (RNAPII)-dependent genes requires the participation of a host of basal transcription factors. Among genes requiring RNAPII for transcription, small nuclear RNAs (snRNAs) display a further requirement for a factor known as snRNA-activating protein complex (SNAPc). The scope of the biological function of SNAPc and its requirement for transcription of protein-coding genes has not been elucidated. To determine the genome-wide occupancy of SNAPc, we performed chromatin immunoprecipitation followed by high-throughput sequencing using antibodies against SNAPC4 and SNAPC1 subunits. Interestingly, while SNAPC4 occupancy was limited to snRNA genes, SNAPC1 chromatin residence extended beyond snRNA genes to include a large number of transcriptionally active protein-coding genes. Notably, SNAPC1 occupancy on highly active genes mirrored that of elongating RNAPII extending through the bodies and 3' ends of protein-coding genes. Inhibition of transcriptional elongation resulted in the loss of SNAPC1 from the 3' ends of genes, reflecting a functional association between SNAPC1 and elongating RNAPII. Importantly, while depletion of SNAPC1 had a small effect on basal transcription, it diminished the transcriptional responsiveness of a large number of genes to two distinct extracellular stimuli, epidermal growth factor (EGF) and retinoic acid (RA). These results highlight a role for SNAPC1 as a general transcriptional coactivator that functions through elongating RNAPII.
authors.affiliation: The Wistar Institute, Philadelphia, Pennsylvania, USA.
authors.forename: David
authors.initials: D
authors.lastname: Baillat
authors.forename: Alessandro
authors.initials: A
authors.lastname: Gardini
authors.forename: Matteo
authors.initials: M
authors.lastname: Cesaroni
authors.forename: Ramin
authors.initials: R
authors.lastname: Shiekhattar
mesh_terms: D020413:3' Untranslated Regions; D047369:Chromatin Immunoprecipitation; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D015894:Genome, Human; D006367:HeLa Cells; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D016366:Open Reading Frames; D010880:Piperidines / Q000494:pharmacology; D012319:RNA Polymerase II / Q000235:genetics* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D012342:RNA, Small Nuclear / Q000235:genetics / Q000378:metabolism; D061805:Transcription Elongation, Genetic / Q000187:drug effects; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology
chemical_list: D020413:3' Untranslated Regions; D004268:DNA-Binding Proteins; D005419:Flavonoids; D010880:Piperidines; D034741:RNA, Small Interfering; D012342:RNA, Small Nuclear; C093069:SNAPC1 protein, human; C116351:SNAPC4 protein, human; D014157:Transcription Factors; C077990:alvocidib; D014212:Tretinoin; D004815:Epidermal Growth Factor; D012319:RNA Polymerase II