PLoS Genetics, Journal Year: 2024, Volume and Issue: 20(12), P. e1011495 - e1011495

Published: Dec. 5, 2024

Copper (Cu) is essential for respiration, neurotransmitter synthesis, oxidative stress response, and transcription regulation, with imbalances leading to neurological, cognitive, muscular disorders. Here we show the role of a novel Cu-binding protein (Cu-BP) in mammalian transcriptional specifically on skeletal muscle differentiation using murine primary myoblasts. Utilizing synchrotron X-ray fluorescence-mass spectrometry, identified cysteine-rich intestinal 2 (mCrip2) as key Cu-BP abundant both nuclear cytosolic fractions. mCrip2 binds two four Cu+ ions high affinity presents limited redox potential. CRISPR/Cas9-mediated deletion impaired myogenesis, likely due Cu accumulation cells. CUT&RUN transcriptome analyses revealed its association gene promoters, including MyoD1 metallothioneins, suggesting Cu-responsive regulatory mCrip2. Our work describes significance metal homeostasis, expanding understanding Cu-network various cellular processes, respiration but can cause serious health issues. This study reveals new involved development Using unbiased metalloproteomic techniques throughput sequencing, found cell nuclei cytoplasm. up has Deleting CRISPR/Cas9 disrupted formation accumulation. Further showed that regulates expression genes like MyoD1, differentiation, metallothioneins response copper supplementation. research highlights importance providing insights into

Language: Английский