Replication landscape of the human genome.

作者: Nataliya Petryk , Malik Kahli , Yves d'Aubenton-Carafa , Yan Jaszczyszyn , Yimin Shen

DOI: 10.1038/NCOMMS10208

关键词: Origin of replicationLicensing factorOkazaki fragmentsPre-replication complexEvolutionary biologyEnhancerGeneticsOrigin recognition complexChromatinBiologyDNA replication

摘要: Despite intense investigation, human replication origins and termini remain elusive. Existing data have shown strong discrepancies. Here we sequenced highly purified Okazaki fragments from two cell types and, for the first time, quantitated fork directionality delineated initiation termination zones genome-wide. Replication initiates stochastically, primarily within non-transcribed, broad (up to 150 kb) that often abut transcribed genes, terminates dispersively between them. progression is significantly co-oriented with transcription. Initiation are frequently contiguous, sometimes separated by regions of unidirectional replication. enriched in open chromatin enhancer marks, even when not flanked border 'topologically associating domains' (TADs). origin recognition complex (ORC)-binding sites better align previously mapped using bubble-trap than λ-exonuclease. This novel panorama reveals how transcription modulate process create cell-type-specific programs.

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