David M Gilbert

Publications (109) View all

• Article: The Replication Domain Model: regulating replicon firing in the context of large-scale chromosome architecture.

  Benjamin D Pope, David M Gilbert
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  ABSTRACT: The "Replicon Theory" of Jacob, Brenner and Cuzin has reliably served as the paradigm for regulating the sites where individual replicons initiate replication. Concurrent with the replicon model was Taylor's demonstration that plant and animal chromosomes replicate segmentally in a defined temporal sequence, via cytologically defined units too large to be accounted for by a single replicon. Instead, there seemed to be a program to choreograph when chromosome units replicate during S phase, executed by inititation at clusters of individual replicons within each segment. Here, we summarize recent molecular evidence for the existence of such units, now known as "replication domains", and discuss how the organization of large chromosomes into structural units has added additional layers of regulation to the original replicon model.
  Journal of Molecular Biology 04/2013; · 4.00 Impact Factor
• Article: SnapShot: Replication Timing.

  Benjamin D Pope, Oscar M Aparicio, David M Gilbert
  Cell 03/2013; 152(6):1390-1390.e1. · 32.40 Impact Factor
• Article: Development of a single-cell array for large-scale DNA fluorescence in situ hybridization.

  Yingru Liu, Brett Kirkland, James Shirley, Zhibin Wang, Peipei Zhang, Jacquelyn Stembridge, Wilson Wong, Shin-Ichiro Takebayashi, David M Gilbert, Steven Lenhert, Jingjiao Guan
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  ABSTRACT: DNA fluorescence in situ hybridization (FISH) is a powerful cytogenetic assay, but conventional sample-preparation methods for FISH do not support large-scale high-throughput data acquisition and analysis, which are potentially useful for several biomedical applications. To address this limitation, we have developed a novel FISH sample-preparation method based on generating a centimetre-sized cell array, in which all cells are precisely positioned and separated from their neighbours. This method is simple and capable of patterning nonadherent human cells. We have successfully performed DNA FISH on the single-cell arrays, which facilitates analysis of the FISH results with the FISH-FINDER computer program.
  Lab on a Chip 02/2013; · 5.67 Impact Factor
• Article: Developmental control of replication timing defines a new breed of chromosomal domains with a novel mechanism of chromatin unfolding.

  Shin-Ichiro Takebayashi, Tyrone Ryba, David M Gilbert
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  ABSTRACT: We recently identified a set of chromosome domains that are early replicating uniquely in pluripotent cells. Their switch from early to late replication occurs just prior to germ layer commitment, associated with a stable form of gene silencing that is difficult to reverse. Here, we discuss results demonstrating that these domains are among the least sensitive regions in the genome to global digestion by either MNase or restriction enzymes. This inaccessible chromatin state persists whether these regions are in their physically distended early replicating or compact late replicating configuration, despite dramatic changes in 3D chromatin folding and long-range chromatin interactions, and despite large changes in transcriptional activity. This contrasts with the strong correlation between early replication, accessibility, transcriptional activity and open chromatin configuration that is observed genome-wide. We put these results in context with findings from other studies indicating that many structural (DNA sequence) and functional (density and activity of replication origins) properties of developmentally regulated replication timing ("switching") domains resemble properties of constitutively late replicating domains. This suggests that switching domains are a type of late replicating domain within which both replication timing and transcription are subject to unique or additional layers of control not experienced by the bulk of the genome. We predict that understanding the unusual structure of these domains will reveal a novel principle of chromosome folding.
  Nucleus (Austin, Texas) 09/2012; 3(6).
• Article: An encyclopedia of mouse DNA elements (Mouse ENCODE).

  John A Stamatoyannopoulos, Michael Snyder, Ross Hardison, Bing Ren, Thomas Gingeras, David M Gilbert, Mark Groudine, Michael Bender, Rajinder Kaul, Theresa Canfield, [......], Melissa S Cline, Vanessa M Kirkup, Katrina Learned, Kate R Rosenbloom, W James Kent, Elise A Feingold, Peter J Good, Michael Pazin, Rebecca F Lowdon, Leslie B Adams
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  ABSTRACT: To complement the human Encyclopedia of DNA Elements (ENCODE) project and to enable a broad range of mouse genomics efforts, the Mouse ENCODE Consortium is applying the same experimental pipelines developed for human ENCODE to annotate the mouse genome.
  Genome biology 08/2012; 13(8):418. · 6.63 Impact Factor