Language
English
Publication Date
6-1-2026
Journal
Genesis
DOI
10.1002/dvg.70062
PMID
42310856
PMCID
PMC13276015
PubMedCentral® Posted Date
6-17-2026
PubMedCentral® Full Text Version
Post-print
Abstract
TWIST1 encodes a highly conserved basic helix–loop–helix transcription factor essential for embryonic development from Drosophila to humans. TWIST1 activity is regulated by post‐translational modifications, including phosphorylation during development and cancer metastasis. Recent cancer studies identified acetylation of lysines K73 and K76 as a novel regulatory modification that shifts TWIST1 from a repressive to an activating state during epithelial‐to‐mesenchymal transition (EMT). However, the developmental and in vivo functions of TWIST1 acetylation remain unknown. To investigate the physiological role, we generated the first acetyl‐deficient Twist1 K73,76R K73,76R and acetyl‐mimic Twist1 K73,76Q K73,76Q mouse models using CRISPR/Cas9‐mediated genome editing. Targeted sequencing confirmed substitutions, and founders were backcrossed onto a C57BL/6J genetic background. Phenotypic analysis revealed that Twist1 acetyl‐deficient mice exhibited highly penetrant craniofacial abnormalities, including severe mandibular hypoplasia, mandibular bone fusion, replacement of premaxillary, maxillary, and palatine bones with cartilage, ectopic cartilage‐like structures, ocular malformations, and reduced skull mineralization. In contrast, acetyl‐mimic mutant embryos displayed milder craniofacial defects characterized by reduced mandibular condylar processes and palatine bones, along with decreased skull mineralization. These findings demonstrate that TWIST1 acetylation at K73 and K76 plays a crucial role in normal craniofacial skeletogenesis, supporting prior cancer studies showing reduced oncogenic activity following loss of TWIST1 acetylation.
Keywords
Animals, Twist-Related Protein 1, Mice, Acetylation, Nuclear Proteins, Craniofacial Abnormalities, Female, Mice, Inbred C57BL, Epithelial-Mesenchymal Transition, Protein Processing, Post-Translational
Published Open-Access
yes
Recommended Citation
Elmeniawi, Mary; Yu, Xiaobin; Wen, Samuel; et al., "Generation and Characterization of Twist1 Acetyl-Mimic and Acetyl-Deficient Mouse Models" (2026). Faculty, Staff and Students Publications. 7093.
https://digitalcommons.library.tmc.edu/baylor_docs/7093