ArticleMolecular and cellular biology2006
The assembly and maintenance of heterochromatin initiated by transgene repeats are independent of the RNA interference pathway in mammalian cells.
Article in Molecular and cellular biology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 52 citations in OpenAlex.
- The sound of silence: Transgene silencing in mammalian cell engineering.Cell systems · 2022Review
- Review
- Modulation of C-to-T mutation by recombination-independent pairing of closely positioned DNA repeats.Biophysical journal · 2021Article
- Histone H2A phosphorylation recruits topoisomerase IIα to centromeres to safeguard genomic stability.The EMBO journal · 2020Article
- Article
- HP1 cooperates with CAF-1 to compact heterochromatic transgene repeats in mammalian cells.Scientific reports · 2018Article
- Partition of Repeat-Induced Point Mutations Reveals Structural Aspects of Homologous DNA-DNA Pairing.Biophysical journal · 2018Article
- Epigenetic Repeat-Induced Gene Silencing in the Chromosomal and Extrachromosomal Contexts in Human Cells.PloS one · 2016Article
- Epigenetic modifications in sex heterochromatin of vole rodents.Chromosoma · 2015Article
- Requirement for CRIF1 in RNA interference and Dicer-2 stability.RNA biology · 2014Article
- MAR-mediated integration of plasmid vectors for in vivo gene transfer and regulation.BMC molecular biology · 2013Article
- Co-transcriptional regulation of alternative pre-mRNA splicing.Biochimica et biophysica acta · 2012Review
- Complexity of RNA polymerase II elongation dynamics.Biochimica et biophysica acta · 2012Review
- dsRNA expression in the mouse elicits RNAi in oocytes and low adenosine deamination in somatic cells.Nucleic acids research · 2012Article
- Fast transcription rates of RNA polymerase II in human cells.EMBO reports · 2011Article
- The distribution of repressive histone modifications on silenced FMR1 alleles provides clues to the mechanism of gene silencing in fragile X syndrome.Human molecular genetics · 2010Article
- Transcription-dependent silencing of inducible convergent transgenes in transgenic mice.Epigenetics & chromatin · 2010Article
- Frequency and spectrum of genomic integration of recombinant adeno-associated virus serotype 8 vector in neonatal mouse liver.Journal of virology · 2008Article
- Cell cycle regulated transcription of heterochromatin in mammals vs. fission yeast: functional conservation or coincidence?Cell cycle (Georgetown, Tex.) · 2008Article
- A mammalian microRNA cluster controls DNA methylation and telomere recombination via Rbl2-dependent regulation of DNA methyltransferases.Nature structural & molecular biology · 2008Article
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Authors and funding
6 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A role for the RNA interference (RNAi) pathway in the establishment of heterochromatin is now well accepted for various organisms. Less is known about its relevance and precise role in mammalian cells. We previously showed that tandem insertion of a 1,000-copy inducible transgene into the genome of baby hamster kidney (BHK) cells initiated the formation of an extremely condensed chromatin locus. Here, we characterized the inactive transgenic locus as heterochromatin, since it was associated with heterochromatin protein 1 (HP1), histone H3 trimethylated at lysine 9, and cytosine methylation in CpG dinucleotides. Northern blot analysis did not detect any transgene-derived small RNAs. RNAi-mediated Dicer knockdown did not disrupt the heterochromatic transgenic locus or up-regulate transgene expression. Moreover, neither Dicer knockdown nor overexpression of transgene-directed small interfering RNAs altered the bidirectional transition of the transgenic locus between the heterochromatic and euchromatic states. Interestingly, tethering of HP1 to the transgenic locus effectively induced transgene silencing and chromatin condensation in a Dicer-independent manner, suggesting a role for HP1 in maintaining the heterochromatic locus. Our results suggest that the RNAi pathway is not required for the assembly and maintenance of noncentromeric heterochromatin initiated by tandem transgene repeats in mammalian cells.
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