COCA-seq: genome-wide mapping of O-GlcNAc-associated open chromatin.

Area of Science:

• Biochemistry
• Genomics
• Epigenetics

Background:

• O-GlcNAcylation is a key post-translational modification affecting gene regulation.
• Accessible chromatin is crucial for O-GlcNAc-mediated transcriptional control.
• Current methods lack the resolution to study O-GlcNAc and chromatin accessibility interplay.

Purpose of the Study:

• To develop a genome-wide method for profiling O-GlcNAc-associated chromatin accessibility.
• To investigate the role of O-GlcNAc-mediated chromatin changes in breast cancer doxorubicin resistance.

Main Methods:

• Developed and validated COCA-seq (Chemoselective Profiling of O-GlcNAc-Associated Chromatin Accessibility).
• Applied COCA-seq to breast cancer models.
• Integrated COCA-seq with bulk RNA-seq for multiomics analysis.

Main Results:

• COCA-seq demonstrates high chemoselectivity and open chromatin specificity.
• Identified key regulatory genes and transcription factors in doxorubicin resistance.
• Uncovered O-GlcNAc-associated open chromatin mechanisms in drug efflux and stress homeostasis.

Conclusions:

• COCA-seq is a versatile tool for mapping O-GlcNAc-associated open chromatin genome-wide.
• O-GlcNAc-associated open chromatin plays a significant role in orchestrating tumor drug resistance.
• This work provides insights into glycosylation's role in cancer biology.