Mouse anti-Human CDON monoclonal antibody, clone 3H23

Myoblast fusion (MF) is required for muscle growth and repair, and its alteration contributes to muscle diseases. The mechanisms governing this process are incompletely understood, and no epigenetic regulator has been previously described. Ash1L is an epigenetic activator belonging to the Trithorax group of proteins and is involved in FSHD muscular dystrophy, autism and cancer. Its physiological role in skeletal muscle is unknown. Here we report that Ash1L expression is positively correlated with MF and reduced in Duchenne muscular dystrophy. In vivo, ex vivo and in vitro experiments support a selective and evolutionary conserved requirement for Ash1L in MF. RNA-and ChIP-sequencing indicate that Ash1L is required to counteract Polycomb repressive activity to allow activation of selected myogenesis genes, in particular the key MF gene Cdon. Our results promote Ash1L as an important epigenetic regulator of MF and suggest that its activity could be targeted to improve cell therapy for muscle diseases.

Weight gain is a possible side effect of the pharmacological antidepressant treatments. Defining antidepressant prescriptions based on personal genetic makeups would decrease the risk of weight gain and increase the quality of the current antidepressant pharmacological treatments. 643 depressed, citalopram treated individuals with available clinical and genome-wide genetic information were investigated to identify the molecular pathways associated with weight gain. 111 individuals experienced weight gain during citalopram treatment. The axon guidance (p.adjust = 0.005) and the developmental biology pathway (p.adjust = 0.01) were enriched in variations associated with weight gain. The developmental biology pathway includes molecular cascades involved in the regulation of beta-cell development, and the transcriptional regulation of white adipocyte differentiation. A number of variations were harbored by genes whose products are involved in the synthesis of collagen (COL4A3, COL5A1 and ITGA1), activity of the thyroid-hormones (NCOR1 and NCOR2), energy metabolism (AD1POQ, PPARGCIA) and myogenic differentiation (CDON). A molecular pathway analysis conducted in a sample of depressed patients identified new candidate genes whose future investigation may provide insights in the molecular events that drive weight gain during antidepressant treatment. (C) 2016 Elsevier Ireland Ltd. All rights reserved.