OGT mediates O-GlcNAcylation of MEIS2 and affects palatal osteogenic development DOI
Junqing Ma, Zhongyin Zhang, Zhi‐Xin Shan

и другие.

Research Square (Research Square), Год журнала: 2025, Номер unknown

Опубликована: Май 15, 2025

Abstract Post-translational modifications (PTMs) in congenital malformations like cleft palate are gradually being elucidated. It has been shown that O-GlcNAcylation as a dynamic PTM of proteins regulates various critical biological processes such transcription, translation and cell fate determination. In this study, substantial decline was detected O-linked β-D-N-acetylglucosamine (O-GlcNAc) levels within the palatine plates all-trans retinoic acid (atRA)-induced mice. The role O-GlcNAc transferase (OGT), sole O-GlcNAc, process palatal development investigated. zebrafish model, absence resulted an elevated prevalence compromised bone formation. Mechanistically, myeloid ecotropic viral integration site 2 (MEIS2), which is mediated by OGT, osteogenesis homeostasis inhibiting stability MEIS2, key gene osteogenesis, via ubiquitination inhibition. Notably, serine 237 residue (Ser237) MEIS2 also identified for O-GlcNAcylation. present study uncovers important function thus establishes novel theoretical framework regulatory network development. This finding may provide avenues future diagnosis prevention palate.

Язык: Английский

Functional genomic profiling of O-GlcNAc reveals its context-specific interplay with RNA polymerase II DOI Creative Commons
Sofia Rucli, Nicolas Descostes, Yulia G. Ermakova

и другие.

Genome biology, Год журнала: 2025, Номер 26(1)

Опубликована: Март 24, 2025

Abstract Background How reversible glycosylation of DNA-bound proteins acts on transcription remains scarcely understood. O-linked β-N-acetylglucosamine (O-GlcNAc) is the only known form modifying nuclear proteins, including RNA polymerase II (RNA Pol II) and many factors. Yet, regulatory function O-GlcNAc modification in mammalian chromatin unclear. Results Here, we combine genome-wide profiling O-GlcNAc-modified with perturbations intracellular glycosylation, II-degron, super-resolution microscopy. Genomic shows a non-random distribution across genome, high densities heterochromatin regions as well actively transcribed gene promoters. Large-scale intersection signal at promoters public ChIP-seq datasets identifies overlap specific cofactors. Knockdown Transferase ( Ogt ) that most direct target genes are downregulated, supporting global positive role cellular genes. Rapid degradation results decrease levels encoding factors DNA enzymes. depletion also unexpectedly causes an increase set for machinery. Conclusions This study provides deconvoluted genomic murine human cells. Perturbations or uncover context-specific reciprocal functional interplay between machinery modification.

Язык: Английский

Процитировано

0
OGT mediates O-GlcNAcylation of MEIS2 and affects palatal osteogenic development DOI
Junqing Ma, Zhongyin Zhang, Zhi‐Xin Shan

и другие.

Research Square (Research Square), Год журнала: 2025, Номер unknown

Опубликована: Май 15, 2025

Abstract Post-translational modifications (PTMs) in congenital malformations like cleft palate are gradually being elucidated. It has been shown that O-GlcNAcylation as a dynamic PTM of proteins regulates various critical biological processes such transcription, translation and cell fate determination. In this study, substantial decline was detected O-linked β-D-N-acetylglucosamine (O-GlcNAc) levels within the palatine plates all-trans retinoic acid (atRA)-induced mice. The role O-GlcNAc transferase (OGT), sole O-GlcNAc, process palatal development investigated. zebrafish model, absence resulted an elevated prevalence compromised bone formation. Mechanistically, myeloid ecotropic viral integration site 2 (MEIS2), which is mediated by OGT, osteogenesis homeostasis inhibiting stability MEIS2, key gene osteogenesis, via ubiquitination inhibition. Notably, serine 237 residue (Ser237) MEIS2 also identified for O-GlcNAcylation. present study uncovers important function thus establishes novel theoretical framework regulatory network development. This finding may provide avenues future diagnosis prevention palate.

Язык: Английский

Процитировано

0