title: Comparative genomics using teleost fish helps to systematically identify target gene bodies of functionally defined human enhancers.
abstract: BACKGROUND
  Human genome is enriched with thousands of conserved non-coding elements (CNEs). Recently, a medium throughput strategy was employed to analyze the ability of human CNEs to drive tissue specific expression during mouse embryogenesis. These data led to the establishment of publicly available genome wide catalog of functionally defined human enhancers. Scattering of enhancers over larger regions in vertebrate genomes seriously impede attempts to pinpoint their precise target genes. Such associations are prerequisite to explore the significance of this in vivo characterized catalog of human enhancers in development, disease and evolution.
  
  
  RESULTS
  This study is an attempt to systematically identify the target gene-bodies for functionally defined human CNE-enhancers. For the purpose we adopted the orthology/paralogy mapping approach and compared the CNE induced reporter expression with reported endogenous expression pattern of neighboring genes. This procedure pinpointed specific target gene-bodies for the total of 192 human CNE-enhancers. This enables us to gauge the maximum genomic search space for enhancer hunting: 4 Mb of genomic sequence around the gene of interest (2 Mb on either side). Furthermore, we used human-rodent comparison for a set of 159 orthologous enhancer pairs to infer that the central nervous system (CNS) specific gene expression is closely associated with the cooperative interaction among at least eight distinct transcription factors: SOX5, HFH, SOX17, HNF3β, c-FOS, Tal1beta-E47S, MEF and FREAC.
  
  
  CONCLUSIONS
  In conclusion, the systematic wiring of cis-acting sites and their target gene bodies is an important step to unravel the role of in vivo characterized catalog of human enhancers in development, physiology and medicine.
authors: National Center for Bioinformatics, Program of Comparative and Evolutionary Genomics, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad 45320, Pakistan.
authors: Nazia
authors: N
authors: Parveen
authors: Ayesha
authors: A
authors: Masood
authors: Nouman
authors: N
authors: Iftikhar
authors: Bushra F
authors: BF
authors: Minhas
authors: Rashid
authors: R
authors: Minhas
authors: Uzma
authors: U
authors: Nawaz
authors: Amir Ali
authors: AA
authors: Abbasi
mesh_terms: D000818:Animals; D017124:Conserved Sequence / Q000235:genetics*; D004742:Enhancer Elements, Genetic; D005399:Fishes / Q000235:genetics; D005786:Gene Expression Regulation; D015894:Genome, Human; D006801:Humans; D051379:Mice; D009928:Organ Specificity / Q000235:genetics; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics*; D014714:Vertebrates / Q000235:genetics