Chromatin signatures of the Drosophila replication program.

Published

Journal Article

DNA replication initiates from thousands of start sites throughout the Drosophila genome and must be coordinated with other ongoing nuclear processes such as transcription to ensure genetic and epigenetic inheritance. Considerable progress has been made toward understanding how chromatin modifications regulate the transcription program; in contrast, we know relatively little about the role of the chromatin landscape in defining how start sites of DNA replication are selected and regulated. Here, we describe the Drosophila replication program in the context of the chromatin and transcription landscape for multiple cell lines using data generated by the modENCODE consortium. We find that while the cell lines exhibit similar replication programs, there are numerous cell line-specific differences that correlate with changes in the chromatin architecture. We identify chromatin features that are associated with replication timing, early origin usage, and ORC binding. Primary sequence, activating chromatin marks, and DNA-binding proteins (including chromatin remodelers) contribute in an additive manner to specify ORC-binding sites. We also generate accurate and predictive models from the chromatin data to describe origin usage and strength between cell lines. Multiple activating chromatin modifications contribute to the function and relative strength of replication origins, suggesting that the chromatin environment does not regulate origins of replication as a simple binary switch, but rather acts as a tunable rheostat to regulate replication initiation events.

Full Text

Duke Authors

Cited Authors

  • Eaton, ML; Prinz, JA; MacAlpine, HK; Tretyakov, G; Kharchenko, PV; MacAlpine, DM

Published Date

  • February 2011

Published In

Volume / Issue

  • 21 / 2

Start / End Page

  • 164 - 174

PubMed ID

  • 21177973

Pubmed Central ID

  • 21177973

Electronic International Standard Serial Number (EISSN)

  • 1549-5469

Digital Object Identifier (DOI)

  • 10.1101/gr.116038.110

Language

  • eng

Conference Location

  • United States