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2016 ; 7
(ä): 10208
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Replication landscape of the human genome
#MMPMID26751768
Petryk N
; Kahli M
; d'Aubenton-Carafa Y
; Jaszczyszyn Y
; Shen Y
; Silvain M
; Thermes C
; Chen CL
; Hyrien O
Nat Commun
2016[Jan]; 7
(ä): 10208
PMID26751768
show ga
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 replication fork directionality and delineated initiation and
termination zones genome-wide. Replication initiates stochastically, primarily
within non-transcribed, broad (up to 150?kb) zones that often abut transcribed
genes, and terminates dispersively between them. Replication fork progression is
significantly co-oriented with the transcription. Initiation and termination
zones are frequently contiguous, sometimes separated by regions of unidirectional
replication. Initiation zones are enriched in open chromatin and enhancer marks,
even when not flanked by genes, and often border 'topologically associating
domains' (TADs). Initiation zones are enriched in origin recognition complex
(ORC)-binding sites and better align to origins previously mapped using
bubble-trap than ?-exonuclease. This novel panorama of replication reveals how
chromatin and transcription modulate the initiation process to create
cell-type-specific replication programs.