[特邀报告]Perturbing TET2 condensation promotes aberrant genome-wide DNA methylation and curtails leukemia cell growth

Perturbing TET2 condensation promotes aberrant genome-wide DNA methylation and curtails leukemia cell growth
编号:82 稿件编号:6 访问权限:仅限参会人 更新:2024-10-27 17:10:38 浏览:86次 特邀报告

报告开始:2024年11月02日 17:50 (Asia/Shanghai)

报告时间:20min

所在会议:[S4] 分会场一:三维基因组学与细胞生物学 / 三维基因组与相分离 » [S4-1] 分会场一:三维基因组学与细胞生物学 /三维基因组与相分离

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摘要
The Ten-eleven Translocation (TET) family of dioxygenases maintain stable local DNA demethylation during cell division and lineage specification. As the major catalytic product of TET enzymes, 5-hydroxymethylcytosine (5hmC) is selectively enriched at specific genomic regions, such as enhancers, in a tissue-dependent manner. However, the mechanisms underlying this selectivity remain unresolved. Here, we unveil a low complexity insert (LCI) domain within TET2 that facilitates its biomolecular condensation with epigenetic modulators, such as ubiquitously transcribedtetratricopeptide repeat on chromosome X (UTX) and mixed-lineage leukemia 4 (MLL4). This co-condensation fosters a permissive chromatin environment for precise DNA demethylation. Disrupting LCI-mediated condensation alters genomic binding of TET2 to cause promiscuous DNA demethylation and genome reorganization. These changes influence the expression of key genes implicated in leukemogenesis to curtail leukemia cell proliferation. Collectively, this study establishesthe pivotal role of TET2 condensation in orchestrating precise DNA demethylation and gene transcription to support tumor cell growth.
关键字
TET2,phase separation,3D genome,DNA hydroxymethylation
报告人
李佳 (Jia Li)
广州实验室 (Guangzhou National Laboratory)

稿件作者
李佳 广州国家实验室;呼吸疾病全国重点实验室
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