Mapping out the regulatory code of the human genome using synthetic biology

Mapping out the regulatory code of the human genome using synthetic biology

Gene regulation is a complex process involving a wide range of molecular components and mechanisms. We know that enhancers regulate gene expression through binding of transcription factors. Grossman et al. published a comprehensive study of enhancers and transcription factors using a synthetic biology approach.  The authors used a technique called massively parallel reporter assay, which uses thousands of natural and synthetic promoters. Using the technique, the contribution of genetic motifs and chromatin states on enhancer activity was studied. Additive and interaction effects between transcription factors and enhancers were found and known interactions in the literature were reproduced. The study greatly extends the known biology of PPAR-γ (peroxisome proliferator-activated receptors) and their role in adipogenesis (formation of fat tissue).

This is an interesting study coming out of the lab of the well-known geneticist Eric S. Lander (spearheaded the human genome project, called evil genius by some).

Regulatory genetics resources

  • VISTA Enhancer Browser – experimentally validated human and mouse noncoding elements
  • Human enhancer atlas – annotation of enhancers in the human hg19 genome
  • Integrated human enhancer database – a centralized on-line repository of predicted enhancers derived from multiple human cell-lines
  • FANTOM5 – functional annotation of the mammalian genome
  • JASPAR – contains a curated, non-redundant set of profiles, derived from published collections of experimentally defined transcription factor binding sites for eukaryotes

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