Takao Nammo

Publications (2)35.53 Total impact

• Article: Mapping open chromatin with formaldehyde-assisted isolation of regulatory elements.

  Takao Nammo, Santiago A Rodríguez-Seguí, Jorge Ferrer
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  ABSTRACT: Noncoding regulatory genomic elements are central for cellular function, differentiation, and disease, but remain poorly characterized. FAIRE (formaldehyde-assisted isolation of regulatory elements) has emerged as a simple method to identify and analyze active regulatory sequences based on their decreased nucleosomal content. More recently FAIRE was combined with high-throughput sequencing (FAIRE-seq) to locate tissue-specific regulatory elements at a genome scale in purified human pancreatic islets. Here we describe the implementation of the FAIRE method in human pancreatic islet cells.
  Methods in molecular biology (Clifton, N.J.) 01/2011; 791:287-96.
• Article: A map of open chromatin in human pancreatic islets.

  Kyle J Gaulton, Takao Nammo, Lorenzo Pasquali, Jeremy M Simon, Paul G Giresi, Marie P Fogarty, Tami M Panhuis, Piotr Mieczkowski, Antonio Secchi, Domenico Bosco, Thierry Berney, Eduard Montanya, Karen L Mohlke, Jason D Lieb, Jorge Ferrer
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  ABSTRACT: Tissue-specific transcriptional regulation is central to human disease. To identify regulatory DNA active in human pancreatic islets, we profiled chromatin by formaldehyde-assisted isolation of regulatory elements coupled with high-throughput sequencing (FAIRE-seq). We identified approximately 80,000 open chromatin sites. Comparison of FAIRE-seq data from islets to that from five non-islet cell lines revealed approximately 3,300 physically linked clusters of islet-selective open chromatin sites, which typically encompassed single genes that have islet-specific expression. We mapped sequence variants to open chromatin sites and found that rs7903146, a TCF7L2 intronic variant strongly associated with type 2 diabetes, is located in islet-selective open chromatin. We found that human islet samples heterozygous for rs7903146 showed allelic imbalance in islet FAIRE signals and that the variant alters enhancer activity, indicating that genetic variation at this locus acts in cis with local chromatin and regulatory changes. These findings illuminate the tissue-specific organization of cis-regulatory elements and show that FAIRE-seq can guide the identification of regulatory variants underlying disease susceptibility.
  Nature Genetics 03/2010; 42(3):255-9. · 35.53 Impact Factor