Fine-tuning of gene expression through the Mettl3-Mettl14-Dnmt1 axis controls ESC differentiation.

The marking of DNA, histones, and RNA is central to gene expression regulation in development and disease. Recent evidence links N6-methyladenosine (mA), installed on RNA by the METTL3-METTL14 methyltransferase complex, to histone modifications, but the link between mA and DNA methylation remains scarcely explored. This study shows that METTL3-METTL14 recruits the DNA methyltransferase DNMT1 to chromatin for gene-body methylation.

The impact of demoralization on the stability of personality traits in a clinical sample.

This study examined whether reductions in the severity of personality disorders (PD) mainly reflect changes in personality traits or rather an alleviation of a demoralized state involving nonspecific unpleasant affect. We used 4 years of longitudinal data from the Collaborative Longitudinal Personality Disorders Study, in which patients ( = 419) completed the Neuroticism-Extraversion-Openness Personality Inventory-Revised (NEO-PI-R) three times over 4 years (at baseline and at 6-month and 4-year follow-up assessments). We compared the NEO Demoralization scale with NEO-PI-R domain scales adjusted for demoralization-related items to determine whether changes in demoralization are more pronounced than changes in adjusted personality traits.

Histone H3 mutations and their impact on genome stability maintenance.

Histones are essential for maintaining chromatin structure and function. Histone mutations lead to changes in chromatin compaction, gene expression, and the recruitment of DNA repair proteins to the DNA lesion. These disruptions can impair critical DNA repair pathways, such as homologous recombination and non-homologous end joining, resulting in increased genomic instability, which promotes an environment favorable to tumor development and progression.

The Portuguese version of the self-report form of the DSM-5 Level of Personality Functioning Scale (LPFS-SR) in a community and clinical sample.

The Level of Personality Functioning Scale-Self-Report (LPFS-SR) operationalizes Criterion A of the DSM-5 Alternative Model for Personality Disorders. The current study aimed 1) to examine the internal consistency of the Portuguese version of the LPFS-SR in a community sample and a clinical sample, 2) to compare non-clinical participants (N = 282, Mage = 48.01, SD = 10.

C-terminally phosphorylated p27 activates self-renewal driver genes to program cancer stem cell expansion, mammary hyperplasia and cancer.

In many cancers, a stem-like cell subpopulation mediates tumor initiation, dissemination and drug resistance. Here, we report that cancer stem cell (CSC) abundance is transcriptionally regulated by C-terminally phosphorylated p27 (p27pT157pT198). Mechanistically, this arises through p27 co-recruitment with STAT3/CBP to gene regulators of CSC self-renewal including MYC, the Notch ligand JAG1, and ANGPTL4.