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

  1. Alexei Tulin,
  2. Dianne Stewart, and
  3. Allan C. Spradling1
  4. Howard Hughes Medical Research Laboratories, Department of Embryology, Carnegie Institution of Washington, Baltimore, Maryland 21210, USA

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.

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