An interplay between BRD4 and G9a regulates skeletal myogenesis.

Histone acetylation and methylation are epigenetic modifications that are dynamically regulated by chromatin modifiers to precisely regulate gene expression. However, the interplay by which histone modifications are synchronized to coordinate cellular differentiation is not fully understood. In this study, we demonstrate a relationship between BRD4, a reader of acetylation marks, and G9a, a writer of methylation marks in the regulation of myogenic differentiation.

Agrin-Matrix Metalloproteinase-12 axis confers a mechanically competent microenvironment in skin wound healing.

An orchestrated wound healing program drives skin repair via collective epidermal cell proliferation and migration. However, the molecular determinants of the tissue microenvironment supporting wound healing remain poorly understood. Herein we discover that proteoglycan Agrin is enriched within the early wound-microenvironment and is indispensable for efficient healing.

Mitchell-Riley syndrome iPSCs exhibit reduced pancreatic endoderm differentiation due to a mutation in .

Mitchell-Riley syndrome (MRS) is caused by recessive mutations in the regulatory factor X6 gene () and is characterised by pancreatic hypoplasia and neonatal diabetes. To determine why individuals with MRS specifically lack pancreatic endocrine cells, we micro-CT imaged a 12-week-old foetus homozygous for the nonsense mutation c.1129C>T, which revealed loss of the pancreas body and tail.

Identification of Quinolinols as Activators of TEAD-Dependent Transcription.

The transcriptional co-regulators YAP (Yes-associated protein) and TAZ (transcriptional coactivator with PDZ-binding motif) are the vertebrate downstream effectors of the Hippo signaling pathway that controls various physiological and pathological processes. YAP and TAZ pair with the TEAD (TEA domain) family of transcription factors to initiate transcription. We previously identified a tractable pocket in TEADs, which has been physiologically shown to bind palmitate.

Therapeutic Targeting of RNA Splicing Catalysis through Inhibition of Protein Arginine Methylation.

Cancer-associated mutations in genes encoding RNA splicing factors (SFs) commonly occur in leukemias, as well as in a variety of solid tumors, and confer dependence on wild-type splicing. These observations have led to clinical efforts to directly inhibit the spliceosome in patients with refractory leukemias. Here, we identify that inhibiting symmetric or asymmetric dimethylation of arginine, mediated by PRMT5 and type I protein arginine methyltransferases (PRMTs), respectively, reduces splicing fidelity and results in preferential killing of SF-mutant leukemias over wild-type counterparts.