Transcriptional Silencing of Nonsense Codon-Containing Immunoglobulin Minigenes

Bühler, Marc; Mohn, Fabio; Stalder, Lukas; Mühlemann, Oliver

doi:10.1016/j.molcel.2005.03.030

Cited by 64 publications

(75 citation statements)

References 47 publications

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“…The levels of histone acetylation are reversibly controlled by the balanced counteraction of histone acetyltransferases (HATs) and histone deacetylases (HDACs). Although HDAC inhibitor treatment have been used to reverse the heterochromatin silencing of Ig minigenes 29 , these drugs are potent inhibitors of the 3 0 RR in B cells. Thus, treatment of B cells with the HDAC inhibitor trichostatin A represses IgH gene transcription, CSR and Ig synthesis in B splenocytes 30 .…”

Section: ′Rr-deficientmentioning

confidence: 99%

Elucidation of IgH 3′ region regulatory role during class switch recombination via germline deletion

et al. 2015

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In mature B cells, class switch recombination (CSR) replaces the expressed constant Cm gene with a downstream C H gene. How the four transcriptional enhancers of the IgH 3 0 regulatory region (3 0 RR) control CSR remains an open question. We have investigated IgG 1 CSR in 3 0 RR-deficient mice. Here we show that the 3 0 RR enhancers target the S g1 acceptor region (and poorly the S m donor region) by acting on epigenetic marks, germline transcription, paused RNA Pol II recruitment, R loop formation, AID targeting and double-strand break generation. In contrast, location and diversity of S m -S g1 junctions are not affected by deletion of the 3 0 RR enhancers. Thus, the 3 0 RR controls the first steps of CSR by priming the S acceptor region but is not implicated in the choice of the end-joining pathway.

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Section: ′Rr-deficientmentioning

confidence: 99%

Elucidation of IgH 3′ region regulatory role during class switch recombination via germline deletion

et al. 2015

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“…Furthermore, the process involves changes to the histone code, involving alteration in methylation status of histone tails (e.g. dimethylation of lysine 9 of histone 3 (H3K9me2) and trimethylation of lysine 27 of histone 3), and the recruitment of both histone deacetylase-3 (HDAC3) and the polycomb group protein, enhancer of zeste homolog 2 (10,17,19,21,22). These changes are consistent with the formation of repressive chromatin structure (17,19,28).…”

mentioning

confidence: 99%

Closed Chromatin Architecture Is Induced by an RNA Duplex Targeting the HIV-1 Promoter Region

Suzuki

Juelich²,

Lim

et al. 2008

Journal of Biological Chemistry

105

144

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In some mammalian systems small interfering RNAs (siRNA) targeting homologous sequences in promoter regions of genes induce transcriptional gene silencing (TGS). We have previously reported the induction of TGS by an siRNA (prom-A siRNA) targeting the tandem NF-B-binding motifs within the human immunodeficiency virus, type 1 (HIV-1), promoter region. Here we report that induction of TGS by prom-A siRNA is accompanied by immediate and sustained local recruitment of Argonaute-1 (Ago1), histone deacetylase-1 (HDAC1), and induction of dimethylation of histone 3 at lysine 9 (H3K9me2), processes known to be associated with transcriptional silencing. Elevated levels of H3K9me2 and HDAC1 spread upstream of the target sequence, and elevated H3K9me2 levels also spread downstream into the coding region. Moreover, this siRNA induces an immediate change in DNA accessibility to restriction enzyme digestion in the region of the transcription initiation site of the HIV-1. This change in accessibility is because of the relocation of a nucleosome known to be associated with this region of the integrated pro-virus. Although there is a theoretical possibility that the observed viral suppression could be mediated by the PTGS mechanism with this siRNA acting at the 3-long term repeat of the virus, we demonstrate that this siRNA, and three other U3 targeted siRNAs, are inefficient inducers of PTGS. These data strongly suggest that siRNA targeting the promoter region acts predominantly at a site within the 5-long term repeat of HIV to induce transcriptional silencing and alterations to chromatin structure of the HIV promoter region that extend well beyond the immediate siRNA target site. These induced changes are consistent with those described in latent HIV-1 infection.

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“…Also known as Thex1 in some species, Eri1 and its ability to inhibit short interfering RNA (siRNA)-directed gene silencing is evolutionarily conserved from Schizosaccharomyces pombe to humans [1][2][3][4] . Because Eri1 encodes a DEDDh-type exonuclease with RNase activity toward the 3′ ends of RNA in vitro 1,[4][5][6] , it was proposed that Eri1 counteracts the RNAi pathway by degrading siRNAs 7 .…”

mentioning

confidence: 99%

Mouse Eri1 interacts with the ribosome and catalyzes 5.8S rRNA processing

Ansel

Pastor

Rath

et al. 2008

Nat Struct Mol Biol

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Eri1 is a 3′-to-5′ exoribonuclease conserved from fission yeast to humans. Here we show that Eri1 associates with ribosomes and ribosomal RNA (rRNA). Ribosomes from Eri1-deficient mice contain 5.8S rRNA that is aberrantly extended at its 3′ end, and Eri1, but not a catalytically inactive mutant, converts this abnormal 5.8S rRNA to the wild-type form in vitro and in cells. In human and murine cells, Eri1 localizes to the cytoplasm and nucleus, with enrichment in the nucleolus, the site of preribosome biogenesis. RNA binding residues in the Eri1 SAP and linker domains promote stable association with rRNA and thereby facilitate 5.8S rRNA 3′ end processing. Taken together, our findings indicate that Eri1 catalyzes the final trimming step in 5.8S rRNA processing, functionally and spatially connecting this regulator of RNAi with the basal translation machinery.

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Transcriptional Silencing of Nonsense Codon-Containing Immunoglobulin Minigenes

Cited by 64 publications

References 47 publications

Elucidation of IgH 3′ region regulatory role during class switch recombination via germline deletion

Elucidation of IgH 3′ region regulatory role during class switch recombination via germline deletion

Closed Chromatin Architecture Is Induced by an RNA Duplex Targeting the HIV-1 Promoter Region

Mouse Eri1 interacts with the ribosome and catalyzes 5.8S rRNA processing

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