The Drosophila heterochromatic gene encoding poly(ADP-ribose) polymerase (PARP) is required to modulate chromatin structure during development

Alexei Tulin, Dianne Stewart, Allan C. Spradling

Research output: Contribution to journalArticlepeer-review

Abstract

Poly(ADP-ribose) polymerase (PARP) is a major NAD-dependent modifying enzyme that mediates important steps in DNA repair, transcription, and apoptosis, but its role during development is poorly understood. We found that a single Drosophila Parp gene spans more than 150 kb of transposon-rich centromeric heterochromatin and produces several differentially spliced transcripts, including a novel isoform, PARP-e, predicted to encode a protein lacking enzymatic activity. An insertion mutation near the upstream promoter for Parp-e disrupts all Parp expression. Heterochromatic but not euchromatic sequences become hypersensitive to micrococcal nuclease, nucleoli fail to form, and transcript levels of the copia retrotransposon are elevated more than 50-fold; the variegated expression of certain transgenes is dominantly enhanced. Larval lethality can be rescued and PARP activity restored by expressing a cDNA encoding PARP-e. We propose that PARP-e autoregulates Parp transcription by influencing the chromatin structure of its heterochromatic environment. Our results indicate that Parp plays a fundamental role organizing the structure of Drosophila chromatin.

Original languageEnglish (US)
Pages (from-to)2108-2119
Number of pages12
JournalGenes & development
Volume16
Issue number16
DOIs
StatePublished - Aug 15 2002
Externally publishedYes

Keywords

  • Chromatin
  • Copia
  • Drosophila
  • Heterochromatin
  • Nucleolus
  • PARP

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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