title: Heat shock factor binding in Alu repeats expands its involvement in stress through an antisense mechanism.
abstract: BACKGROUND
  Alu RNAs are present at elevated levels in stress conditions and, consequently, Alu repeats are increasingly being associated with the physiological stress response. Alu repeats are known to harbor transcription factor binding sites that modulate RNA pol II transcription and Alu RNAs act as transcriptional co-repressors through pol II binding in the promoter regions of heat shock responsive genes. An observation of a putative heat shock factor (HSF) binding site in Alu led us to explore whether, through HSF binding, these elements could further contribute to the heat shock response repertoire.
  
  
  RESULTS
  Alu density was significantly enriched in transcripts that are down-regulated following heat shock recovery in HeLa cells. ChIP analysis confirmed HSF binding to a consensus motif exhibiting positional conservation across various Alu subfamilies, and reporter constructs demonstrated a sequence-specific two-fold induction of these sites in response to heat shock. These motifs were over-represented in the genic regions of down-regulated transcripts in antisense oriented Alus. Affymetrix Exon arrays detected antisense signals in a significant fraction of the down-regulated transcripts, 50% of which harbored HSF sites within 5 kb. siRNA knockdown of the selected antisense transcripts led to the over-expression, following heat shock, of their corresponding down-regulated transcripts. The antisense transcripts were significantly enriched in processes related to RNA pol III transcription and the TFIIIC complex.
  
  
  CONCLUSIONS
  We demonstrate a non-random presence of Alu repeats harboring HSF sites in heat shock responsive transcripts. This presence underlies an antisense-mediated mechanism that represents a novel component of Alu and HSF involvement in the heat shock response.
authors: Genomics and Molecular Medicine, Institute of Genomics and Integrative Biology, Council of Scientific and Industrial Research (CSIR-IGIB), Delhi- India.
authors: Rajesh
authors: R
authors: Pandey
authors: Amit K
authors: AK
authors: Mandal
authors: Vineet
authors: V
authors: Jha
authors: Mitali
authors: M
authors: Mukerji
mesh_terms: D020087:Alu Elements / Q000235:genetics*; D016375:Antisense Elements (Genetics); D001665:Binding Sites; D015536:Down-Regulation; D020869:Gene Expression Profiling; D006367:HeLa Cells; D006360:Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism; D018869:Heat-Shock Response / Q000235:genetics; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D011485:Protein Binding; D012320:RNA Polymerase III / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D019474:Transcription Factors, TFIII / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D000098832:Transcription Factor TFIIIC
chemical_list: D016375:Antisense Elements (Genetics); D006360:Heat-Shock Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D019474:Transcription Factors, TFIII; D000098832:Transcription Factor TFIIIC; D012320:RNA Polymerase III