E-box independent chromatin recruitment turns MYOD into a transcriptional repressor.

MYOD is an E-box sequence-specific basic Helix-Loop-Helix (bHLH) transcriptional activator that, when expressed in non-muscle cells, induces nuclear reprogramming toward skeletal myogenesis by promoting chromatin accessibility at previously silent loci. Here, we report on the identification of a previously unrecognized property of MYOD as repressor of gene expression, via E-box-independent chromatin binding within accessible genomic elements, which invariably leads to reduced chromatin accessibility. MYOD-mediated repression requires the integrity of functional domains previously implicated in MYOD-mediated activation of gene expression.

Disulfide Tethering to Map Small Molecule Binding Sites Transcriptome-wide.

We report the development of Tether-seq, a transcriptome-wide screen to probe RNA-small molecule interactions using disulfide tethering. This technique uses sU metabolic labeling to provide sites for reversible and covalent attachment of small molecule disulfides to the transcriptome. By screening under reducing conditions, we identify interactions that are stabilized by binding over those driven by the reactivity of the RNA sites.

Acetyl-methyllysine marks chromatin at active transcription start sites.

Lysine residues in histones and other proteins can be modified by post-translational modifications that encode regulatory information. Lysine acetylation and methylation are especially important for regulating chromatin and gene expression. Pathways involving these post-translational modifications are targets for clinically approved therapeutics to treat human diseases.