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

White, Eric J. (author)
Emanuelsson, Olof (author)
Yale University
Scalzo, David (author)
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Royce, Thomas (author)
Kosak, Steven (author)
Oakeley, Edward J. (author)
Weissman, Sherman (author)
Gerstein, Mark (author)
Groudine, Mark (author)
Snyder, Michael (author)
Schübeler, Dirk (author)
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 (creator_code:org_t)
2004-12-10
2004
English.
In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 101:51, s. 17771-17776
  • Journal article (peer-reviewed)
Abstract Subject headings
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  • 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.

Subject headings

NATURVETENSKAP  -- Biologi -- Bioinformatik och systembiologi (hsv//swe)
NATURAL SCIENCES  -- Biological Sciences -- Bioinformatics and Systems Biology (hsv//eng)

Keyword

HUMAN-CHROMOSOMES
TRANSCRIPTIONAL ACTIVIT
MICROARRAY DATA
R-BANDS
GENOME
GENE
ASSOCIATION
LYMPHOCYTES
PATTERN
REGION

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ref (subject category)
art (subject category)

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