Integrative analysis of gene amplification in Drosophila follicle cells: parameters of origin activation and repression.

Published

Journal Article

In metazoans, how replication origins are specified and subsequently activated is not well understood. Drosophila amplicons in follicle cells (DAFCs) are genomic regions that undergo rereplication to increase DNA copy number. We identified all DAFCs by comparative genomic hybridization, uncovering two new amplicons in addition to four known previously. The complete identification of all DAFCs enabled us to investigate these in vivo replicons with respect to parameters of transcription, localization of the origin recognition complex (ORC), and histone acetylation, yielding important insights into gene amplification as a metazoan replication model. Significantly, ORC is bound across domains spanning 10 or more kilobases at the DAFC rather than at a specific site. Additionally, ORC is bound at many regions that do not undergo amplification, and, in contrast to cell culture, these regions do not correlate with high gene expression. As a developmental strategy, gene amplification is not the predominant means of achieving high expression levels, even in cells capable of amplification. Intriguingly, we found that, in some strains, a new amplicon, DAFC-22B, does not amplify, a consequence of distant repression of ORC binding and origin activation. This repression is alleviated when a fragment containing the origin is placed in different genomic contexts.

Full Text

Duke Authors

Cited Authors

  • Kim, JC; Nordman, J; Xie, F; Kashevsky, H; Eng, T; Li, S; MacAlpine, DM; Orr-Weaver, TL

Published Date

  • July 2011

Published In

Volume / Issue

  • 25 / 13

Start / End Page

  • 1384 - 1398

PubMed ID

  • 21724831

Pubmed Central ID

  • 21724831

Electronic International Standard Serial Number (EISSN)

  • 1549-5477

International Standard Serial Number (ISSN)

  • 0890-9369

Digital Object Identifier (DOI)

  • 10.1101/gad.2043111

Language

  • eng