Double-strand breaks in facultative heterochromatin require specific movements and chromatin changes for efficient repair

Nature Communications, vol. 15, pp. 8984

Abstract

DNA double-strand breaks (DSBs) must be properly repaired within diverse chromatin domains to maintain genome stability. Whereas euchromatin has an open structure and is associated with transcription, facultative heterochromatin is essential to silence developmental genes and forms compact nuclear condensates, called polycomb bodies. Whether the specific chromatin properties of facultative heterochromatin require distinct DSB repair mechanisms remains unknown. Here, we integrate single DSB systems in euchromatin and facultative heterochromatin in Drosophila melanogaster and find that heterochromatic DSBs rapidly move outside polycomb bodies. These DSB movements coincide with a break-proximal reduction in the canonical heterochromatin mark histone H3 Lysine 27 trimethylation (H3K27me3). We demonstrate that DSB movement and loss of H3K27me3 at heterochromatic DSBs depend on the histone demethylase dUtx. Moreover, loss of dUtx specifically disrupts completion of homologous recombination at heterochromatic DSBs. We conclude that DSBs in facultative heterochromatin require dUtx-mediated loss of H3K27me3 to promote DSB movement and repair.

Authors 8

1. Marieke R. Wensveen

   Utrecht University · University Medical Center Utrecht

   Affiliation as printed

   Center for Molecular Medicine, University Medical Center Utrecht, Universiteitsweg 100, Utrecht, the Netherlands

2. Aditya A. Dixit

   Utrecht University · University Medical Center Utrecht

   Affiliation as printed

   Center for Molecular Medicine, University Medical Center Utrecht, Universiteitsweg 100, Utrecht, the Netherlands

3. Robin van Schendel Aachen Human Genetics Department

   Leiden University Medical Center

   Affiliation as printed

   Human Genetics Department, Leiden University Medical Center, Leiden, the Netherlands

4. Apfrida Kendek

   Utrecht University · University Medical Center Utrecht

   Affiliation as printed

   Center for Molecular Medicine, University Medical Center Utrecht, Universiteitsweg 100, Utrecht, the Netherlands

5. Jan-Paul Lambooij

   Utrecht University · University Medical Center Utrecht

   Affiliation as printed

   Center for Molecular Medicine, University Medical Center Utrecht, Universiteitsweg 100, Utrecht, the Netherlands

6. Marcel Tijsterman Aachen Human Genetics Department

   Leiden University Medical Center

   Affiliation as printed

   Human Genetics Department, Leiden University Medical Center, Leiden, the Netherlands

7. Serafin U. Colmenares

   University of California, Berkeley

   Affiliation as printed

   Department of Molecular and Cell Biology, University of California Berkeley, Berkeley, USA

8. Aniek Janssen corresponding

   University Medical Center Utrecht

   Affiliation as printed

   Center for Molecular Medicine, University Medical Center Utrecht, Universiteitsweg 100, Utrecht, the Netherlands. a.janssen-2@umcutrecht.nl