tretinoin and alvocidib

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.

Topics: 3' Untranslated Regions; Chromatin Immunoprecipitation; DNA-Binding Proteins; Epidermal Growth Factor; Flavonoids; Genome, Human; HeLa Cells; High-Throughput Nucleotide Sequencing; Humans; Oligonucleotide Array Sequence Analysis; Open Reading Frames; Piperidines; RNA Polymerase II; RNA, Small Interfering; RNA, Small Nuclear; Transcription Elongation, Genetic; Transcription Factors; Tretinoin

Topics: Antineoplastic Agents; Azacitidine; Biomedical Research; Carbazoles; Carboplatin; Cytarabine; Daunorubicin; Decitabine; Enzyme Inhibitors; Etoposide; Flavonoids; Furans; Humans; Leukemia, Myeloid, Acute; Mitoxantrone; Piperidines; Quinolones; Staurosporine; Topotecan; Tretinoin