Abstract
Drosophila melanogaster heterochromatin protein 1 (HP1a or HP1)1 is believed to be involved in active transcription, transcriptional gene silencing and the formation of heterochromatin2,3,4,5,6,7. But little is known about the function of HP1 during development. Using a Gal4-induced RNA interference system, we showed that conditional depletion of HP1 in transgenic flies resulted in preferential lethality in male flies. Cytological analysis of mitotic chromosomes showed that HP1 depletion caused sex-biased chromosomal defects, including telomere fusions. The global levels of specific histone modifications, particularly the hallmarks of active chromatin, were preferentially increased in males as well. Expression analysis showed that approximately twice as many genes were specifically regulated by HP1 in males than in females. Furthermore, HP1-regulated genes showed greater enrichment for HP1 binding in males. Taken together, these results indicate that HP1 modulates chromosomal integrity, histone modifications and transcription in a sex-specific manner.
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Acknowledgements
We thank S.C.R. Elgin for providing us with monoclonal (C1A9) and polyclonal (rabbit #192) antibodies against D. melanogaster HP1; G. Reuter for providing antibody against D. melanogaster Su(var)3-9; E. Giordano for sharing unpublished information; G. Rueter for providing antibody against D. melanogaster Su(var)3-9; D. Schübeler and A. Peters for their critical reading of the manuscript; and S. Oakeley and H. Rothnie for their help on nomenclature. This work was supported by the Novartis Research Foundation.
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Supplementary information
Supplementary Fig. 1
Western and immunofluorescent detection of histone modifications in wild type and HP1-depleted larval cells. (PDF 287 kb)
Supplementary Fig. 2
The specificity of HP1 antibodies is determined by western and immunofluorescence. (PDF 178 kb)
Supplementary Table 1
Genes affected both in males and females. (PDF 232 kb)
Supplementary Table 2
Genes specifically affected in males. (PDF 361 kb)
Supplementary Table 3
Genes specifically affected in females. (PDF 231 kb)
Supplementary Table 4
Primers used to perform ChIP and RT-PCR. (PDF 27 kb)
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Liu, LP., Ni, JQ., Shi, YD. et al. Sex-specific role of Drosophila melanogaster HP1 in regulating chromatin structure and gene transcription. Nat Genet 37, 1361–1366 (2005). https://doi.org/10.1038/ng1662
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DOI: https://doi.org/10.1038/ng1662
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