A mutant ASXL1-EHMT complex contributes to heterochromatin dysfunction in clonal hematopoiesis and chronic monomyelocytic leukemia.

Unlabelled: is one of the three most frequently mutated genes in age-related clonal hematopoiesis (CH), alongside and . CH can progress to myeloid malignancies including chronic monomyelocytic leukemia (CMML), and is also strongly associated with inflammatory cardiovascular disease and all-cause mortality in humans. DNMT3A and TET2 regulate DNA methylation and demethylation pathways respectively, and loss-of-function mutations in these genes reduce DNA methylation in heterochromatin, allowing de-repression of silenced elements in heterochromatin.

A mutant ASXL1-BAP1-EHMT complex contributes to heterochromatin dysfunction in clonal hematopoiesis and chronic monomyelocytic leukemia.

is one of the three most frequently mutated genes in age-related clonal hematopoiesis (CH), alongside and (. CH can progress to myeloid malignancies including chronic monomyelocytic leukemia (CMML) and is also strongly associated with inflammatory cardiovascular disease and all-cause mortality in humans. DNMT3A and TET2 regulate DNA methylation and demethylation pathways, respectively, and loss-of-function mutations in these genes reduce DNA methylation in heterochromatin, allowing derepression of silenced elements in heterochromatin.

Management of Persistent Left Superior Vena Cava: Overcoming Lead and Vascular Complications With Transcatheter Pacing System Implantation.

Isolated persistent left superior vena cava (PLSVC) is a rare congenital anomaly typically found incidentally due to its asymptomatic nature. However, it can present technical challenges for device implanters. We report a case involving a patient with PLSVC, for whom the implantation of a transcatheter pacing system proved to be the most effective long-term solution.

The Role of Fatty Acid Synthase in the Vascular Smooth Muscle Cell to Foam Cell Transition.

Vascular smooth muscle cells (VSMCs), in their contractile and differentiated state, are fundamental for maintaining vascular function. Upon exposure to cholesterol (CHO), VSMCs undergo dedifferentiation, adopting characteristics of foam cells-lipid-laden, macrophage-like cells pivotal in atherosclerotic plaque formation. CHO uptake by VSMCs leads to two primary pathways: ABCA1-mediated efflux or storage in lipid droplets as cholesterol esters (CEs).

OGT prevents DNA demethylation and suppresses the expression of transposable elements in heterochromatin by restraining TET activity genome-wide.

The GlcNAc transferase OGT interacts robustly with all three mammalian TET methylcytosine dioxygenases. We show here that deletion of the gene in mouse embryonic stem cells (mESC) results in a widespread increase in the TET product 5-hydroxymethylcytosine (5hmC) in both euchromatic and heterochromatic compartments, with concomitant reduction of the TET substrate 5-methylcytosine (5mC) at the same genomic regions. mESC engineered to abolish the TET1-OGT interaction likewise displayed a genome-wide decrease of 5mC.