j1 mouse embryonic stem cells were grown on gamma - irradiated mouse embryonic fibroblasts cells under standard conditions ( 85% high glucose dmem , 15% hyclone fbs , 0.1 mm non - essential amino acids , 0.1 mm -mercaptoethanol , 1 mm glutamine , lif 500u / ml , + p / s ) . before harvesting for hi - c , j1 mescs were passaged onto feeder free 0.2% gelatin coated plates for at least 2 passages to rid the culture of feeder cells . harvesting the cells for hi - c was performed as previously described , with the only modification being that the adherent cell cultures were dissociated with trypsin prior to fixation . hi - c analysis and paired end libraries were prepared as previously described and sequenced on the illumina hi - seq2000 platform . reads were mapped to reference human ( hg18 ) or mouse genomes ( mm9 ) , and non - mapping reads and pcr duplicates were removed . 2-dimensional heat - maps were generated as previously described . for detailed descriptions of the data analysis , including descriptions of the directionality index , hidden markov models , dynamic interactions identification , and boundary overlap between cells and across species , see supplemental methods . j1 mouse embryonic stem cells were grown on gamma - irradiated mouse embryonic fibroblasts cells under standard conditions ( 85% high glucose dmem , 15% hyclone fbs , 0.1 mm non - essential amino acids , 0.1 mm -mercaptoethanol , 1 mm glutamine , lif 500u / ml , + p / s ) . before harvesting for hi - c , j1 mescs were passaged onto feeder free 0.2% gelatin coated plates for at least 2 passages to rid the culture of feeder cells . harvesting the cells for hi - c was performed as previously described , with the only modification being that the adherent cell cultures were dissociated with trypsin prior to fixation . hi - c analysis and paired end libraries were prepared as previously described and sequenced on the illumina hi - seq2000 platform . reads were mapped to reference human ( hg18 ) or mouse genomes ( mm9 ) , and non - mapping reads and pcr duplicates were removed . for detailed descriptions of the data analysis , including descriptions of the directionality index , hidden markov models , dynamic interactions identification , and boundary overlap between cells and across species , see supplemental methods .
the spatial organization of the genome is intimately linked to its biological function , yet our understanding of higher order genomic structure is coarse , fragmented and incomplete . in the nucleus of eukaryotic cells , 
 interphase chromosomes occupy distinct chromosome territories ( ct ) , and numerous models have been proposed for how chromosomes fold within cts1 . 
 these models , however , provide only few mechanistic details about the relationship between higher order chromatin structure and genome function . 
 recent advances in genomic technologies have led to rapid revolutions in the study of 3d genome organization . 
 in particular , hi - c has been introduced as a method for identifying higher order chromatin interactions genome wide2 . in the present study 
 , we investigated the 3d organization of the human and mouse genomes in embryonic stem cells and terminally differentiated cell types at unprecedented resolution . 
 we identify large , megabase - sized local chromatin interaction domains , which we term  topological domains  , as a pervasive structural feature of the genome organization . 
 these domains correlate with regions of the genome that constrain the spread of heterochromatin . 
 the domains are stable across different cell types and highly conserved across species , suggesting that topological domains are an inherent property of mammalian genomes . 
 lastly , we find that the boundaries of topological domains are enriched for the insulator binding protein ctcf , housekeeping genes , trnas , and sine retrotransposons , suggesting that these factors may play a role in establishing the topological domain structure of the genome .