Defining heterochromatin inC. elegansthrough genome-wide analysis of the heterochromatin protein 1 homolog HPL-2

Jacob M. Garrigues; Simone Sidoli; Benjamin A. Garcia; Susan Strome

doi:10.1101/gr.180489.114

Defining heterochromatin inC. elegansthrough genome-wide analysis of the heterochromatin protein 1 homolog HPL-2

Genome Research ◽

10.1101/gr.180489.114 ◽

2014 ◽

Vol 25 (1) ◽

pp. 76-88 ◽

Cited By ~ 46

Author(s):

Jacob M. Garrigues ◽

Simone Sidoli ◽

Benjamin A. Garcia ◽

Susan Strome

Keyword(s):

Heterochromatin Protein 1 ◽

Heterochromatin Protein ◽

Genome Wide Analysis ◽

Genome Wide

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The Integrity of piRNA Clusters is Abolished by Insulators in the Drosophila Germline

Genes ◽

10.3390/genes10030209 ◽

2019 ◽

Vol 10 (3) ◽

pp. 209 ◽

Cited By ~ 1

Author(s):

Elizaveta Radion ◽

Olesya Sokolova ◽

Sergei Ryazansky ◽

Pavel Komarov ◽

Yuri Abramov ◽

...

Keyword(s):

Binding Sites ◽

Regulatory Elements ◽

Evolutionary Constraints ◽

Heterochromatin Protein 1 ◽

Heterochromatin Protein ◽

Genome Wide Analysis ◽

Genome Wide ◽

Pirna Cluster ◽

A Genome ◽

Cluster Activity

Piwi-interacting RNAs (piRNAs) control transposable element (TE) activity in the germline. piRNAs are produced from single-stranded precursors transcribed from distinct genomic loci, enriched by TE fragments and termed piRNA clusters. The specific chromatin organization and transcriptional regulation of Drosophila germline-specific piRNA clusters ensure transcription and processing of piRNA precursors. TEs harbour various regulatory elements that could affect piRNA cluster integrity. One of such elements is the suppressor-of-hairy-wing (Su(Hw))-mediated insulator, which is harboured in the retrotransposon gypsy. To understand how insulators contribute to piRNA cluster activity, we studied the effects of transgenes containing gypsy insulators on local organization of endogenous piRNA clusters. We show that transgene insertions interfere with piRNA precursor transcription, small RNA production and the formation of piRNA cluster-specific chromatin, a hallmark of which is Rhino, the germline homolog of the heterochromatin protein 1 (HP1). The mutations of Su(Hw) restored the integrity of piRNA clusters in transgenic strains. Surprisingly, Su(Hw) depletion enhanced the production of piRNAs by the domesticated telomeric retrotransposon TART, indicating that Su(Hw)-dependent elements protect TART transcripts from piRNA processing machinery in telomeres. A genome-wide analysis revealed that Su(Hw)-binding sites are depleted in endogenous germline piRNA clusters, suggesting that their functional integrity is under strict evolutionary constraints.

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Genome-wide redistribution of H3K27me3 is linked to genotoxic stress and defective growth

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1511377112 ◽

2015 ◽

Vol 112 (46) ◽

pp. E6339-E6348 ◽

Cited By ~ 40

Author(s):

Evelina Y. Basenko ◽

Takahiko Sasaki ◽

Lexiang Ji ◽

Cameron J. Prybol ◽

Rachel M. Burckhardt ◽

...

Keyword(s):

Topoisomerase I ◽

Normal Growth ◽

Genotoxic Stress ◽

Heterochromatin Protein 1 ◽

Heterochromatin Protein ◽

Heterochromatin Formation ◽

Polycomb Repressive Complex 2 ◽

Genome Wide ◽

Histone H3k27 ◽

Embryonic Ectoderm Development

H3K9 methylation directs heterochromatin formation by recruiting multiple heterochromatin protein 1 (HP1)-containing complexes that deacetylate histones and methylate cytosine bases in DNA. In Neurospora crassa, a single H3K9 methyltransferase complex, called the DIM-5,-7,-9, CUL4, DDB1 Complex (DCDC), is required for normal growth and development. DCDC-deficient mutants are hypersensitive to the genotoxic agent methyl methanesulfonate (MMS), but the molecular basis of genotoxic stress is unclear. We found that both the MMS sensitivity and growth phenotypes of DCDC-deficient strains are suppressed by mutation of embryonic ectoderm development or Su-(var)3-9; E(z); Trithorax (set)-7, encoding components of the H3K27 methyltransferase Polycomb repressive complex-2 (PRC2). Trimethylated histone H3K27 (H3K27me3) undergoes genome-wide redistribution to constitutive heterochromatin in DCDC- or HP1-deficient mutants, and introduction of an H3K27 missense mutation is sufficient to rescue phenotypes of DCDC-deficient strains. Accumulation of H3K27me3 in heterochromatin does not compensate for silencing; rather, strains deficient for both DCDC and PRC2 exhibit synthetic sensitivity to the topoisomerase I inhibitor Camptothecin and accumulate γH2A at heterochromatin. Together, these data suggest that PRC2 modulates the response to genotoxic stress.

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