CBFA2T2: a novel H3K27 reader regulating metabolism and tumor growth
Year: 2026
Type: article
Abstract: Histone H3.3K27M mutations are identified in diffuse midline glioma (DMG), resulting in a global reduction in H3K27me3. Analyzing the histone recognition mechanism at H3K27 position can enhance the understanding of this highly lethal mutation. Here we identify a novel histone reader CBFA2T2, which recognizes non-mutated or un-modified histone H3K27. Biochemical assays confirm this binding specificity, indicating that it is mediated by NHR2 domain of CBFA2T2. CBFA2T2 represses the transcription of metabolic genes involved in carbon metabolism, glycolysis/gluconeogenesis and the TCA cycle pathways through its binding to H3K27, thereby regulating metabolite levels. These alter the alpha-ketoglutarate/Succinate ratio and indirectly impacts H3K27me3 level, through affecting the H3K27me3 demethylases. Our results uncover a novel mechanism by which CBFA2T2 transcriptionally regulates metabolism and tumor growth in H3.3K27M cells. These findings suggest that CBFA2T2 and its targeted genes may serve as potential therapeutic targets for the treatment of H3.3K27M cancer.
Source: Molecular Cancer
Authors: Shengfei He, Yutian Ou, Fangfang Jiao, Jiuxing Feng, Ping Zhu, Jie Ma, Ning Xu, Haitao Li, Rui Guo
Institutions: Shanghai Medical College of Fudan University, Fudan University, Pudong Medical Center, State Key Laboratory of Molecular Oncology, Tsinghua University, Shanghai Jiao Tong University, Shanghai Ninth People's Hospital, Guangdong Academy of Medical Sciences, Guangdong Provincial People's Hospital, Southern Medical University, XinHua Hospital, Shanxi Medical University, Center for Life Sciences
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,090
OpenAlex ID: W7129568649