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CTCF β-hydroxybutyrylation catalyzed by NAT10 regulates MHC-II gene expression
Rui Zhou1, Shirui Li1, Siyi Jiang1
1School of Life Sciences, Chongqing University, Chongqing 401331, China.
None:
The CCCTC-binding factor (CTCF) protein and its posttranslational modifications are critical for gene expression and genome organization, yet the biological significance of CTCF β-hydroxybutyrylation (Kbhb) has remained unclear. In this study, we found that CTCF can interact with N-acetyltransferase 10 (NAT10) and is β-hydroxybutyrylated at lysine 202 (K202) by NAT10. Mechanistically, our results indicate that NAT10 is associated with reduced levels and altered localization of chromatin-bound CTCF in U2OS cells. Functionally, we observed that decreased chromatin-bound CTCF following BHB treatment correlates with changes in MHC-II gene expression in the B-cell line Raji, and that increased BHB levels, induced by streptozotocin (STZ) treatment or fasting, significantly impact MHC-II gene expression in the spleens of mice. These findings suggest a potential role for CTCF β-hydroxybutyrylation in regulating MHC-II gene expression, providing new insights into the possible interplay among metabolic signaling, chromatin dynamics, and gene regulation.
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