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DNA replication-timing analysis of human chromosome 22 at high resolution and different developmental states.

Abstract：

:Duplication of the genome during the S phase of the cell cycle does not occur simultaneously; rather, different sequences are replicated at different times. The replication timing of specific sequences can change during development; however, the determinants of this dynamic process are poorly understood. To gain insights into the contribution of developmental state, genomic sequence, and transcriptional activity to replication timing, we investigated the timing of DNA replication at high resolution along an entire human chromosome (chromosome 22) in two different cell types. The pattern of replication timing was correlated with respect to annotated genes, gene expression, novel transcribed regions of unknown function, sequence composition, and cytological features. We observed that chromosome 22 contains regions of early- and late-replicating domains of 100 kb to 2 Mb, many (but not all) of which are associated with previously described chromosomal bands. In both cell types, expressed sequences are replicated earlier than nontranscribed regions. However, several highly transcribed regions replicate late. Overall, the DNA replication-timing profiles of the two different cell types are remarkably similar, with only nine regions of difference observed. In one case, this difference reflects the differential expression of an annotated gene that resides in this region. Novel transcribed regions with low coding potential exhibit a strong propensity for early DNA replication. Although the cellular function of such transcripts is poorly understood, our results suggest that their activity is linked to the replication-timing program.

journal_name

Proc Natl Acad Sci U S A

journal_title

Proceedings of the National Academy of Sciences of the United States of America

authors

White EJ,Emanuelsson O,Scalzo D,Royce T,Kosak S,Oakeley EJ,Weissman S,Gerstein M,Groudine M,Snyder M,Schübeler D

doi

10.1073/pnas.0408170101

keywords:

subject

Has Abstract

pub_date

2004-12-21 00:00:00

pages

17771-6

issue

eissn

0027-8424

issn

1091-6490

pii

0408170101

journal_volume

101

pub_type

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DNA replication-timing analysis of human chromosome 22 at high resolution and different developmental states.