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Cited by 64Genomics and Chromatin DynamicsChromosomal and Genetic VariationsNuclear Structure and Function

Drosophila melanogaster linker histone dH1 is required for transposon silencing and to preserve genome integrity

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Vujatovic, Olivera, Zaragoza, Katrin, Vaquero, Alejandro, Reina, Oscar, Bernués, Jordi, Azorín, Fernando·2012·Nucleic Acids Research
DOI 10.1093/nar/gks224PMC PMC3384340
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Abstract

Histone H1 is an intrinsic component of chromatin, whose important contribution to chromatin structure is well-established in vitro. Little is known, however, about its functional roles in vivo. Here, we have addressed this question in Drosophila, a model system offering many advantages since it contains a single dH1 variant. For this purpose, RNAi was used to efficiently deplete dH1 in flies. Expression-profiling shows that dH1 depletion affects expression of a relatively small number of genes in a regional manner. Furthermore, depletion up-regulates inactive genes, preferentially those located in heterochromatin, while active euchromatic genes are down-regulated, suggesting that the contribution of dH1 to transcription regulation is mainly structural, organizing chromatin for proper gene-expression regulation. Up-regulated genes are remarkably enriched in transposons. In particular, R1/R2 retrotransposons, which specifically integrate in the rDNA locus, are strongly up-regulated. Actually, depletion increases expression of transposon-inserted rDNA copies, resulting in synthesis of aberrant rRNAs and enlarged nucleolus. Concomitantly, dH1-depleted cells accumulate extra-chromosomal rDNA, show increased γH2Av content, stop proliferation and activate apoptosis, indicating that depletion causes genome instability and affects proliferation. Finally, the contributions to maintenance of genome integrity and cell proliferation appear conserved in human hH1s, as their expression rescues proliferation of dH1-depleted cells.

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Cited by

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Authors
Vujatovic, O., Zaragoza, K., Vaquero, A., Reina, O., Bernués, J., & Azorín, F.
Affiliations
Consejo Superior de Investigaciones Científicas (ES)
ORCID
Venue
Nucleic Acids Research
Publisher
Oxford University Press (OUP)
Published
2012-02-09
Volume
40
Issue
12
Pages
5402-5414
ISSN
  • 0305-1048 (ISSN-L)
  • 1362-4962
DOI
10.1093/nar/gks224
PMC
PMC3384340
OpenAlex
W2156155665
Cited by
64
References
5
Citations by year
2026: 4 · 2025: 5 · 2024: 3 · 2023: 6 · 2022: 4 · 2021: 6 · 2020: 1 · 2019: 5 · 2018: 5 · 2017: 5 · 2016: 3 · 2015: 8 · 2014: 5 · 2013: 4
FWCI
2.19
Type
journal article
Language
en
Open access
Licence
Locations
  • Nucleic Acids Research (publishedVersion, cc-by-nc)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion, cc-by-nc)
  • HighWire Press Open Archive (submittedVersion)
Funders
  • Generalitat de Catalunya (SGR2009‐1023, SGR2009)
  • Ministerio de Ciencia e Innovación (BFU2009-07111, CSD2006‐49)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
Keywords
histone H1, transposon silencing, genome stability, chromatin structure, heterochromatin, ribosomal DNA, nucleolus, genomic instability, apoptosis, cell proliferation, transcriptional regulation, Drosophila melanogaster
MeSH terms
Animals, Drosophila melanogaster, Gene Expression Regulation, Heterochromatin, Histones, Humans, Retroelements, Gene Silencing, Drosophila Proteins, RNA Interference, Genomic Instability, Cell Proliferation, Genome, Insect

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