Open chromatin encoded in DNA sequence is the signature of 'master' replication origins in human cells Export

@article{citeulike:5426159, abstract = {For years, progress in elucidating the mechanisms underlying replication initiation and its coupling to transcriptional activities and to local chromatin structure has been hampered by the small number (approximately 30) of well-established origins in the human genome and more generally in mammalian genomes. Recent in silico studies of compositional strand asymmetries revealed a high level of organization of human genes around 1000 putative replication origins. Here, by comparing with recently experimentally identified replication origins, we provide further support that these putative origins are active in vivo. We show that regions [\~{}]300-kb wide surrounding most of these putative replication origins that replicate early in the S phase are hypersensitive to DNase I cleavage, hypomethylated and present a significant enrichment in genomic energy barriers that impair nucleosome formation (nucleosome-free regions). This suggests that these putative replication origins are specified by an open chromatin structure favored by the DNA sequence. We discuss how this distinctive attribute makes these origins, further qualified as master' replication origins, priviledged loci for future research to decipher the human spatio-temporal replication program. Finally, we argue that these master' origins are likely to play a key role in genome dynamics during evolution and in pathological situations. 10.1093/nar/gkp631}, author = {Audit, Benjamin and Zaghloul, Lamia and Vaillant, Cedric and Chevereau, Guillaume and d'Aubenton-Carafa, Yves and Thermes, Claude and Arneodo, Alain}, citeulike-article-id = {5426159}, citeulike-linkout-0 = {http://dx.doi.org/10.1093/nar/gkp631}, citeulike-linkout-1 = {http://nar.oxfordjournals.org/content/37/18/6064.abstract}, citeulike-linkout-2 = {http://nar.oxfordjournals.org/content/37/18/6064.full.pdf}, citeulike-linkout-3 = {http://view.ncbi.nlm.nih.gov/pubmed/19671527}, citeulike-linkout-4 = {http://www.hubmed.org/display.cgi?uids=19671527}, day = {1}, doi = {10.1093/nar/gkp631}, issn = {1362-4962}, journal = {Nucl. Acids Res.}, keywords = {chromatin-organization, replication}, month = {October}, number = {18}, pages = {6064--6075}, posted-at = {2009-10-20 18:06:40}, priority = {2}, title = {Open chromatin encoded in DNA sequence is the signature of 'master' replication origins in human cells}, url = {http://dx.doi.org/10.1093/nar/gkp631}, volume = {37}, year = {2009} }

TY - JOUR ID - citeulike:5426159 L3 - citeulike-article-id:5426159 N2 - For years, progress in elucidating the mechanisms underlying replication initiation and its coupling to transcriptional activities and to local chromatin structure has been hampered by the small number (approximately 30) of well-established origins in the human genome and more generally in mammalian genomes. Recent in silico studies of compositional strand asymmetries revealed a high level of organization of human genes around 1000 putative replication origins. Here, by comparing with recently experimentally identified replication origins, we provide further support that these putative origins are active in vivo. We show that regions [~]300-kb wide surrounding most of these putative replication origins that replicate early in the S phase are hypersensitive to DNase I cleavage, hypomethylated and present a significant enrichment in genomic energy barriers that impair nucleosome formation (nucleosome-free regions). This suggests that these putative replication origins are specified by an open chromatin structure favored by the DNA sequence. We discuss how this distinctive attribute makes these origins, further qualified as master' replication origins, priviledged loci for future research to decipher the human spatio-temporal replication program. Finally, we argue that these master' origins are likely to play a key role in genome dynamics during evolution and in pathological situations. 10.1093/nar/gkp631 IS - 18 JF - Nucl. Acids Res. SN - 1362-4962 EP - 6075 TI - Open chromatin encoded in DNA sequence is the signature of 'master' replication origins in human cells VL - 37 SP - 6064 KW - chromatin-organization KW - replication AU - Audit, Benjamin AU - Zaghloul, Lamia AU - Vaillant, Cedric AU - Chevereau, Guillaume AU - d'Aubenton-Carafa, Yves AU - Thermes, Claude AU - Arneodo, Alain PY - 2009/10/01/ UR - http://dx.doi.org/10.1093/nar/gkp631 ER -