Requirement for SNAPC1 in transcriptional responsiveness to diverse extracellular signals

Mol Cell Biol. 2012 Nov;32(22):4642-50. doi: 10.1128/MCB.00906-12. Epub 2012 Sep 10.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Chromatin Immunoprecipitation
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Epidermal Growth Factor / pharmacology
  • Flavonoids / pharmacology
  • Genome, Human
  • HeLa Cells
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Oligonucleotide Array Sequence Analysis
  • Open Reading Frames
  • Piperidines / pharmacology
  • RNA Polymerase II / genetics*
  • RNA Polymerase II / metabolism
  • RNA, Small Interfering / genetics
  • RNA, Small Nuclear / genetics
  • RNA, Small Nuclear / metabolism
  • Transcription Elongation, Genetic* / drug effects
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism
  • Tretinoin / pharmacology

Substances

  • 3' Untranslated Regions
  • DNA-Binding Proteins
  • Flavonoids
  • Piperidines
  • RNA, Small Interfering
  • RNA, Small Nuclear
  • SNAPC1 protein, human
  • SNAPC4 protein, human
  • Transcription Factors
  • alvocidib
  • Tretinoin
  • Epidermal Growth Factor
  • RNA Polymerase II