tRNA genes protect a reporter gene from epigenetic silencing in mouse cells

Ebersole, Thomas A.; Kim, Jung-Hyun; Samoshkin, Alexander; Kouprina, Natalay; Pavlı́ček, Adam; White, Robert J.; Larionov, Vladimir

doi:10.4161/cc.10.16.17092

Cited by 52 publications

(53 citation statements)

References 58 publications

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“…For over 30 years, the only known route to intercellular chromosome transmission remains MMCT. This approach is efficient (10 ¡5 ) for alphoid tetO -HAC delivery into various cultured cancer cell types, 15,16,22 but has repeatedly failed for ES cell recipients. After an assessment of a series of modifications of the original microcell mediated chromosome transfer (MMCT) method, however, we have developed a protocol for EGFP-HAC delivery into mouse ES cells, albeit with limited efficiency (10 ¡6 ).…”

Section: Resultsmentioning

confidence: 99%

Stable maintenance of de novo assembled human artificial chromosomes in embryonic stem cells and their differentiated progeny in mice

et al. 2015

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Section: Resultsmentioning

confidence: 99%

Stable maintenance of de novo assembled human artificial chromosomes in embryonic stem cells and their differentiated progeny in mice

et al. 2015

Self Cite

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“…30 Chromatin immunoprecipitation (ChIP) against RNAP III machinery confirms the enrichment of RNAP III, TFIIIB and TFIIIC, and deletion of A-box promoter elements leads to the spread of silencing chromatin, suggesting the recruitment of TFIIIC is also essential for insulator activity in mammalian cells. In humans, tRNA genes also cluster throughout the genome, 31 and share a high degree of syntenic conservation, implying the locations of tDNAs are functionally significant.…”

Section: The Tfiiic Insulator Complexmentioning

confidence: 99%

“…TFIIIC bound ETC sites also possess insulator activity, particularly when multimerized in S. cerevisiae. 16,44 However, multiple orphan B-box elements were unable to exhibit barrier activity in transgenic reporter assays conducted in MEL cells, 30 suggesting additional factors may be necessary for competent insulator function in mammals, or that barrier assays do not accurately reflect the role of endogenous TFIIIC sites.…”

Section: The Tfiiic Insulator Complexmentioning

confidence: 99%

tDNA insulators and the emerging role of TFIIIC in genome organization

Bortle

Corcés

2012

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R ecent findings provide evidence that tDNAs function as chromatin insulators from yeast to humans. TFIIIC, a transcription factor that interacts with the B-box in tDNAs as well as thousands of ETC sites in the genome, is responsible for insulator function. Though tDNAs are capable of enhancer-blocking and barrier activities for which insulators are defined, new insights into the relationship between insulators and chromatin structure suggest that TFIIIC serves a complex role in genome organization. We review the role of tRNA genes and TFIIIC as chromatin insulators, and highlight recent findings that have broadened our understanding of insulators in genome biology.

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“…tRNA gene sequences/Pol III binding have been shown to encode insulators in yeast (15)(16)(17)(18), mouse (19), and human (20,21). The association of insulators to the binding of RNA Pol III, or transcription factor III C (TFIIIC) specifically, to B-box elements is widely observed in multiple species, suggesting that Pol III-related machinery represents another insulator mechanism in addition to CTCF binding.…”

Section: Significancementioning

confidence: 99%

MIR retrotransposon sequences provide insulators to the human genome

Wang

Vicente-García

Seruggia

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

104

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Insulators are regulatory elements that help to organize eukaryotic chromatin via enhancer-blocking and chromatin barrier activity. Although there are several examples of transposable element (TE)-derived insulators, the contribution of TEs to human insulators has not been systematically explored. Mammalian-wide interspersed repeats (MIRs) are a conserved family of TEs that have substantial regulatory capacity and share sequence characteristics with tRNA-related insulators. We sought to evaluate whether MIRs can serve as insulators in the human genome. We applied a bioinformatic screen using genome sequence and functional genomic data from CD4 + T cells to identify a set of 1,178 predicted MIR insulators genome-wide. These predicted MIR insulators were computationally tested to serve as chromatin barriers and regulators of gene expression in CD4 + T cells. The activity of predicted MIR insulators was experimentally validated using in vitro and in vivo enhancer-blocking assays. MIR insulators are enriched around genes of the T-cell receptor pathway and reside at T-cell-specific boundaries of repressive and active chromatin. A total of 58% of the MIR insulators predicted here show evidence of T-cell-specific chromatin barrier and gene regulatory activity. MIR insulators appear to be CCCTC-binding factor (CTCF) independent and show a distinct local chromatin environment with marked peaks for RNA Pol III and a number of histone modifications, suggesting that MIR insulators recruit transcriptional complexes and chromatin modifying enzymes in situ to help establish chromatin and regulatory domains in the human genome. The provisioning of insulators by MIRs across the human genome suggests a specific mechanism by which TE sequences can be used to modulate gene regulatory networks.

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tRNA genes protect a reporter gene from epigenetic silencing in mouse cells

Cited by 52 publications

References 58 publications

Stable maintenance of de novo assembled human artificial chromosomes in embryonic stem cells and their differentiated progeny in mice

Stable maintenance of de novo assembled human artificial chromosomes in embryonic stem cells and their differentiated progeny in mice

tDNA insulators and the emerging role of TFIIIC in genome organization

MIR retrotransposon sequences provide insulators to the human genome

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