Aberrant DNA methylation of ribosomal RNA genes in lung cancer

Teschler, Stefanie; Richter, Antje; Jiménez, Alejandra; Linder, Benedikt; Dammann, Reinhard

doi:10.1055/s-0035-1556658

Cited by 2 publications

(6 citation statements)

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“…We and others have shown that the inactive copies are packed into nucleosomes and contain methylated promoter sequences [ 44 , 45 , 46 ], whereas the transcribed rRNA genes are free of nucleosomes and the rRNA promoter is unmethylated [ 46 , 47 , 48 ]. Therefore, our data as well as other data suggest that, on average, 70% to 90% of the human rDNA repeats are epigenetically inactive [ 13 , 38 ].…”

Section: Resultssupporting

confidence: 83%

“…For example, in hepatocellular carcinoma, hypomethylation of the rDNA promoter has been revealed [ 37 ]. In other cancer tissues (e.g., breast, lung, colorectal and endometrial) hypermethylation of rRNA genes compared to normal tissues has been observed [ 13 , 34 , 38 , 39 , 40 ]. Thus, it will also be interesting to analyze the brain-specific methylation of rDNA in BPD patients.…”

Section: Resultsmentioning

confidence: 99%

“…DNA methylation levels of two rDNA regions (promoter and 5′ETS ) and of PRIMA1 were determined by bisulfite pyrosequencing [ 13 , 19 , 57 ]. Bisulfite treatment of genomic DNA was done as described previously [ 19 ].…”

Section: Methodsmentioning

confidence: 99%

“…About 60% of genes harbor CpG- and GC-rich DNA sequences in their 5′ regulatory region, which are termed CpG island promoters [ 11 ]. Active genes are associated with an open and unmethylated CpG island promoter and hypermethylated CpG islands are correlated with epigenetically silenced genes [ 12 , 13 ]. By changing the cellular profile in the brain's emotional, reward, and memory circuits, these epigenetic modifications have also been linked to perseverant, pathogenic memories typical for post-traumatic stress disorder (PTSD), major depressive disorder (MDD) and BPD [ 10 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

“…Epigenetic deregulation of rRNA genes by aberrant DNA methylation has been found in different human diseases, including cancer [ 13 , 34 , 35 ]. In psychiatric diseases, increased methylation of the regulatory CpG island promoter of rRNA genes has been reported in the brain of suicide persons and this has been correlated with reduced rRNA levels [ 36 ].…”

Section: Introductionmentioning

confidence: 99%

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Aberrant DNA Methylation of rDNA and PRIMA1 in Borderline Personality Disorder

Teschler

Gotthardt

Dammann

et al. 2016

IJMS

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Borderline personality disorder (BPD) is a serious psychic disease with a high risk for suicide. DNA methylation is a hallmark for aberrant epigenetic regulation and could be involved in the etiology of BPD. Previously, it has been reported that increased DNA methylation of neuropsychiatric genes is found in the blood of patients with BPD compared to healthy controls. Here, we analyzed DNA methylation patterns of the ribosomal RNA gene (rDNA promoter region and 5′-external transcribed spacer/5′ETS) and the promoter of the proline rich membrane anchor 1 gene (PRIMA1) in peripheral blood samples of 24 female patients (mean age (33 ± 11) years) diagnosed with DSM-IV BPD and in 11 female controls (mean age (32 ± 7) years). A significant aberrant methylation of rDNA and PRIMA1 was revealed for BPD patients using pyrosequencing. For the promoter of PRIMA1, the average methylation of six CpG sites was 1.6-fold higher in BPD patients compared to controls. In contrast, the methylation levels of the rDNA promoter region and the 5′ETS were significantly lower (0.9-fold) in patients with BPD compared to controls. Thus, for nine CpGs located in the rDNA promoter region and for four CpGs at the 5′ETS decreased methylation was found in peripheral blood of patients compared to controls. Our results suggest that aberrant methylation of rDNA and PRIMA1 is associated with the pathogenesis of BPD.

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Section: Resultssupporting

confidence: 83%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Aberrant DNA Methylation of rDNA and PRIMA1 in Borderline Personality Disorder

Teschler

Gotthardt

Dammann

et al. 2016

IJMS

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Past, present, and future of genetic research in borderline personality disorder

Nia

Eveleth

Gabbay

et al. 2018

Current Opinion in Psychology

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Borderline Personality Disorder (BPD) is a major mental illness with a lifetime prevalence of approximately 1-3%, characterized by a persistent pattern of instability in relationships, mood, impulse regulation, and sense of self. This results in impulsive self-damaging behavior, high suicide rates, and severe functional impairment. BPD has a complex, multifactorial etiology, resulting from an interaction among genetic and environmental substrates, and has moderate to high heritability based on twin and family studies. However, our understanding of the genetic architecture of BPD is very limited. This is a critical obstacle since genetics can pave the way for identifying new treatment targets and developing preventive and disease-modifying pharmacological treatments which are currently lacking. We review genetic studies in BPD, with a focus on limitations and challenges and future directions. Genetic research in BPD is still in its very early stages compared to other major psychiatric disorders. Most early genetic studies in BPD were non-replicated association studies in small samples, focused on single candidate genes. More recently, there has been one genome-wide linkage study and a genome-wide association study (GWAS) of subclinical BPD traits and a first GWAS in a relatively modest sample of patients fulfilling full diagnostic criteria for the disorder. Although there are adequate animal models for some of the core dimensions of BPD, there is a lack of translational research including data from animal models in BPD. Research in more pioneering fields, such as imaging genetics, deep sequencing and epigenetics, holds promise for elucidating the pathophysiology of BPD and identifying new treatment targets.

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Aberrant DNA methylation of ribosomal RNA genes in lung cancer

Cited by 2 publications

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Aberrant DNA Methylation of rDNA and PRIMA1 in Borderline Personality Disorder

Aberrant DNA Methylation of rDNA and PRIMA1 in Borderline Personality Disorder

Past, present, and future of genetic research in borderline personality disorder

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