A distinct epigenetic signature at targets of a leukemia protein

Rossetti, Stefano; Hoogeveen, André T.; Liang, Ping; Stanciu, Cornel N.; Spek, Peter van der; Sacchi, Nicoletta

doi:10.1186/1471-2164-8-38

Cited by 8 publications

(12 citation statements)

References 49 publications

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“…This seemingly controversial result might possibly be explained by a context dependent gene regulation, since Wotton et al used 3T3 murine fibroblast cells in their experiments. In line with our data, PTPRCAP transcription was found to be repressed by RUNX1-MTG8 and - MTG16 fusion genes, two RUNX1 fusions that are frequently found in acute myeloid leukemia [14]. Furthermore, the regulation of two other genes that are differentially expressed in E/R -positive ALL, also concords with our E/R KD results.…”

Section: Resultssupporting

confidence: 92%

The Leukemia-Specific Fusion Gene ETV6/RUNX1 Perturbs Distinct Key Biological Functions Primarily by Gene Repression

et al. 2011

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Background ETV6/RUNX1 (E/R) (also known as TEL/AML1) is the most frequent gene fusion in childhood acute lymphoblastic leukemia (ALL) and also most likely the crucial factor for disease initiation; its role in leukemia propagation and maintenance, however, remains largely elusive. To address this issue we performed a shRNA-mediated knock-down (KD) of the E/R fusion gene and investigated the ensuing consequences on genome-wide gene expression patterns and deducible regulatory functions in two E/R-positive leukemic cell lines.FindingsMicroarray analyses identified 777 genes whose expression was substantially altered. Although approximately equal proportions were either up- (KD-UP) or down-regulated (KD-DOWN), the effects on biological processes and pathways differed considerably. The E/R KD-UP set was significantly enriched for genes included in the “cell activation”, “immune response”, “apoptosis”, “signal transduction” and “development and differentiation” categories, whereas in the E/R KD-DOWN set only the “PI3K/AKT/mTOR signaling” and “hematopoietic stem cells” categories became evident. Comparable expression signatures obtained from primary E/R-positive ALL samples underline the relevance of these pathways and molecular functions. We also validated six differentially expressed genes representing the categories “stem cell properties”, “B-cell differentiation”, “immune response”, “cell adhesion” and “DNA damage” with RT-qPCR.ConclusionOur analyses provide the first preliminary evidence that the continuous expression of the E/R fusion gene interferes with key regulatory functions that shape the biology of this leukemia subtype. E/R may thus indeed constitute the essential driving force for the propagation and maintenance of the leukemic process irrespective of potential consequences of associated secondary changes. Finally, these findings may also provide a valuable source of potentially attractive therapeutic targets.

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Section: Resultssupporting

confidence: 92%

The Leukemia-Specific Fusion Gene ETV6/RUNX1 Perturbs Distinct Key Biological Functions Primarily by Gene Repression

et al. 2011

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“…The aberrant AML1-MTG fusion proteins retain the ability of interplaying with both repressor proteins and/or histone modifying enzymes, and can induce an altered epigenetic status at the chromatin of both coding and non-coding AML1-target genes [ 26 , 27 , 45 ]. Apparently, the fusion of two MTGs, MTG8 and MTG16, to the RHD region of AML1 does not affect the in vitro RNA-binding properties.…”

Section: Discussionmentioning

confidence: 99%

Novel RNA-binding properties of the MTG chromatin regulatory proteins

et al. 2008

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Background: The myeloid translocation gene (MTG) proteins are non-DNA-binding transcriptional regulators capable of interacting with chromatin modifying proteins. As a consequence of leukemia-associated chromosomal translocations, two of the MTG proteins, MTG8 and MTG16, are fused to the DNA-binding domain of AML1, a transcriptional activator crucial for hematopoiesis. The AML1-MTG fusion proteins, as the wild type MTGs, display four conserved homology regions (NHR1-4) related to the Drosophila nervy protein. Structural protein analyses led us to test the hypothesis that specific MTG domains may mediate RNA binding.

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“…AE014133 ) (Ajdic et al, 2002 ) and identified an interesting phenomenon: the rnc gene is located on upstream of vicRKX tricistronic operon. It is suggested that genes located nearby are functionally related and make up a part of a metabolic pathway (Okuda et al, 2007 ). Thus, we hypothesize that rnc may be involved in the regulation of exopolysaccharide synthesis.…”

Section: Introductionmentioning

confidence: 99%

The rnc Gene Promotes Exopolysaccharide Synthesis and Represses the vicRKX Gene Expressions via MicroRNA-Size Small RNAs in Streptococcus mutans

Mao

Yang

et al. 2016

Front. Microbiol.

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Dental caries is a biofilm-dependent disease that largely relies on the ability of Streptococcus mutans to synthesize exopolysaccharides. Although the rnc gene is suggested to be involved in virulence mechanisms in many other bacteria, the information regarding it in S. mutans is very limited. Here, using deletion or overexpression mutant assay, we demonstrated that rnc in S. mutans significantly positively regulated exopolysaccharide synthesis and further altered biofilm formation. Meanwhile, the cariogenecity of S. mutans was decreased by deletion of rnc in a specific pathogen-free (SPF) rat model. Interestingly, analyzing the expression at mRNA level, we found the downstream vic locus was repressed by rnc in S. mutans. Using deep sequencing and bioinformatics analysis, for the first time, three putative microRNA-size small RNAs (msRNAs) targeting vicRKX were predicted in S. mutans. The expression levels of these msRNAs were negatively correlated with vicRKX but positively correlated with rnc, indicating rnc probably repressed vicRKX expression through msRNAs at the post-transcriptional level. In all, the results present that rnc has a potential role in the regulation of exopolysaccharide synthesis and can affect vicRKX expressions via post-transcriptional repression in S. mutans. This study provides an alternative avenue for further research aimed at preventing caries.

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A distinct epigenetic signature at targets of a leukemia protein

Cited by 8 publications

References 49 publications

The Leukemia-Specific Fusion Gene ETV6/RUNX1 Perturbs Distinct Key Biological Functions Primarily by Gene Repression

The Leukemia-Specific Fusion Gene ETV6/RUNX1 Perturbs Distinct Key Biological Functions Primarily by Gene Repression

Novel RNA-binding properties of the MTG chromatin regulatory proteins

The rnc Gene Promotes Exopolysaccharide Synthesis and Represses the vicRKX Gene Expressions via MicroRNA-Size Small RNAs in Streptococcus mutans

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