01867nas a2200145   4500008004100000245008600041210006900127260001300196300001000209490000700219520134300226100001701569700002501586856011001611       2011                        eng d00aStructure determination of genomic domains by satisfaction of spatial restraints.0 aStructure determination of genomic domains by satisfaction of sp  c2011 Jan  a25-350 v193 a<p>The three-dimensional (3D) architecture of a genome is non-random and known to facilitate the spatial colocalization of regulatory elements with the genes they regulate. Determining the 3D structure of a genome may therefore probe an essential step in characterizing how genes are regulated. Currently, there are several experimental and theoretical approaches that aim at determining the 3D structure of genomes and genomic domains; however, approaches integrating experiments and computation to identify the most likely 3D folding of a genome at medium to high resolutions have not been widely explored. Here, we review existing methodologies and propose that the integrative modeling platform ( http://www.integrativemodeling.org ), a computational package developed for structurally characterizing protein assemblies, could be used for integrating diverse experimental data towards the determination of the 3D architecture of genomic domains and entire genomes at unprecedented resolution. Our approach, through the visualization of looping interactions between distal regulatory elements, will allow for the characterization of global chromatin features and their relation to gene expression. We illustrate our work by outlining the recent determination of the 3D architecture of the &alpha;-globin domain in the human genome.</p>1 aBaù, Davide1 aMarti-Renom, Marc, A  uhttp://clinbioinfosspa.es/content/structure-determination-genomic-domains-satisfaction-spatial-restraints01792nas a2200217   4500008004100000245010400041210007000145260001300215300001100228490000700239520104100246100001701287700002001304700002101324700002201345700001501367700002401382700001601406700002501422856012701447       2011                        eng d00aThe three-dimensional folding of the α-globin gene domain reveals formation of chromatin globules.0 athreedimensional folding of the αglobin gene domain reveals form  c2011 Jan  a107-140 v183 a<p>We developed a general approach that combines chromosome conformation capture carbon copy (5C) with the Integrated Modeling Platform (IMP) to generate high-resolution three-dimensional models of chromatin at the megabase scale. We applied this approach to the ENm008 domain on human chromosome 16, containing the &alpha;-globin locus, which is expressed in K562 cells and silenced in lymphoblastoid cells (GM12878). The models accurately reproduce the known looping interactions between the &alpha;-globin genes and their distal regulatory elements. Further, we find using our approach that the domain folds into a single globular conformation in GM12878 cells, whereas two globules are formed in K562 cells. The central cores of these globules are enriched for transcribed genes, whereas nontranscribed chromatin is more peripheral. We propose that globule formation represents a higher-order folding state related to clustering of transcribed genes around shared transcription machineries, as previously observed by microscopy.</p>1 aBaù, Davide1 aSanyal, Amartya1 aLajoie, Bryan, R1 aCapriotti, Emidio1 aByron, Meg1 aLawrence, Jeanne, B1 aDekker, Job1 aMarti-Renom, Marc, A  uhttp://clinbioinfosspa.es/content/three-dimensional-folding-%CE%B1-globin-gene-domain-reveals-formation-chromatin-globules