Transition to naïve human pluripotency mirrors pan-cancer DNA hypermethylation.

Epigenetic reprogramming is a cancer hallmark, but how it unfolds during early neoplastic events and its role in carcinogenesis and cancer progression is not fully understood. Here we show that resetting from primed to naïve human pluripotency results in acquisition of a DNA methylation landscape mirroring the cancer DNA methylome, with gradual hypermethylation of bivalent developmental genes. We identify a dichotomy between bivalent genes that do and do not become hypermethylated, which is also mirrored in cancer.

Mitochondria are required for pro-ageing features of the senescent phenotype.

Cell senescence is an important tumour suppressor mechanism and driver of ageing. Both functions are dependent on the development of the senescent phenotype, which involves an overproduction of pro-inflammatory and pro-oxidant signals. However, the exact mechanisms regulating these phenotypes remain poorly understood.

Correlation of the osteoarthritis susceptibility variants that map to chromosome 20q13 with an expression quantitative trait locus operating on NCOA3 and with functional variation at the polymorphism rs116855380.

Objective: To functionally characterize the osteoarthritis (OA) susceptibility variants that map to a region of high linkage disequilibrium (LD) on chromosome 20q13 marked by the single-nucleotide polymorphism (SNP) rs6094710 and encompassing NCOA3 and SULF2.

Methods: Nucleic acids were extracted from the cartilage of OA patients. Overall and allelic expression of NCOA3 and SULF2 were measured by quantitative reverse transcription-polymerase chain reaction and pyrosequencing, respectively.

Differential DNA methylation and expression of inflammatory and zinc transporter genes defines subgroups of osteoarthritic hip patients.

Objectives: We have previously shown that the cartilage DNA methylome delineates two clusters of osteoarthritic (OA) hip patients, characterised by differential methylation of inflammatory genes, while others have demonstrated a link between zinc homeostasis and inflammation in OA. We aimed to investigate these effects at the methylation and gene expression level.

Methods: We used our previously generated methylation data while quantitative PCR was used to measure gene expression using RNA from the hip cartilage of members of both clusters and from control individuals without hip OA.

Characterization of the cartilage DNA methylome in knee and hip osteoarthritis.

Objective: The aim of this study was to characterize the genome-wide DNA methylation profile of chondrocytes from knee and hip cartilage obtained from patients with osteoarthritis (OA) and hip cartilage obtained from patients with femoral neck fracture, providing the first comparison of DNA methylation between OA and non-OA hip cartilage, and between OA hip and OA knee cartilage.

Methods: The study was performed using the Illumina Infinium HumanMethylation450 BeadChip array, which allows the annotation of ∼480,000 CpG sites. Genome-wide methylation was assessed in chondrocyte DNA extracted from 23 hip OA patients, 73 knee OA patients, and 21 healthy hip control patients with femoral neck fracture.

A novel checkpoint and RPA inhibitory pathway regulated by Rif1.

Cells accumulate single-stranded DNA (ssDNA) when telomere capping, DNA replication, or DNA repair is impeded. This accumulation leads to cell cycle arrest through activating the DNA-damage checkpoints involved in cancer protection. Hence, ssDNA accumulation could be an anti-cancer mechanism.

Epigenetic reprogramming of breast cancer cells with oocyte extracts.

Background: Breast cancer is a disease characterised by both genetic and epigenetic alterations. Epigenetic silencing of tumour suppressor genes is an early event in breast carcinogenesis and reversion of gene silencing by epigenetic reprogramming can provide clues to the mechanisms responsible for tumour initiation and progression. In this study we apply the reprogramming capacity of oocytes to cancer cells in order to study breast oncogenesis.