Presentation/Session Information

Session Information

Session Title: Epigenetics and Gene Regulation Session Type: Parallel
Session Location: Carnesale Palisades Ballroom Session Time: Thu, Jun 25 8:30AM - 11:30AM

Presentation Information

Program Number: 18 Presentation Time: 10:42AM - 10:54AM

Presentation Content

Epigenetic program of DNA replication.Ehsan Pourkarimi, James Bellush, Iestyn Whitehouse. Memorial Sloan-Kettering Cancer Center, New York, New Yo

In eukaryotes, multiple replication origins initiate DNA synthesis bidirectionally. Half of the genome is duplicated discontinuously on the lagging strand in the form of Okazaki Fragments (OFs). Previously we have purified and sequenced OFs from S. cerevisiae, and have demonstrated their utility in mapping genome wide DNA replication patterns (1,2). Despite many years of research, the precise location efficiency and abundance of replication origins in metazoa remains elusive. Here we capture and sequence OFs from C. elegans and generate a genome wide map of DNA replication.

We use a DNA ligation compromised genetic background and purify single stranded OFs from developing embryos. Aligning sequence reads of OFs to the C. elegans genome reveals a characteristic strand bias at specific sites that are approximately 50-100 Kb apart. The complementary enrichment of Okazaki fragments to either the Watson or Crick strands is the hallmark of a replication origin. Additionally we have found that origins of replication in C. elegans are correlated with transcriptionally active regions of chromatin. Using the histone modification data set of modENCODE we found a strong association between replication start sites and acetylation of Histone H3 lysine 27 (H3K27ac). Acetylation of H3K27 is a chromatin mark characteristic of gene enhancer elements. Finally, we show that a partial depletion of CBP/P300 the sole histone H3 acetyltransferase (HAT) responsible for H3K27 acetylation has a profound effect on DNA replication.  

Our data indicate that the DNA replication program is likely plastic and is matched with the transcriptional program. Ultimately our data show, both DNA replication and gene transcription are likely regulated by similar epigenetic processes. 

1. Intrinsic coupling of lagging-strand synthesis to chromatin assembly

Duncan J. Smith& Iestyn Whitehouse. Nature, 2012

2. Quantitative, genome-wide analysis of eukaryotic replication initiation and termination.

McGuffee SR, Smith DJ, Whitehouse I. Mol Cell, 2013.




Please note: Abstract shown here should NOT be cited in bibliographies. Material contained herein should be treated as personal communication and should be cited as such only with the consent of the author.

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