TBC1D3 promotes neural progenitor proliferation by suppressing the histone methyltransferase G9a
Qiong-Qiong Hou, Qi Xiao, Xin-Yao Sun, Xiang-Chun Ju, Zhen‐Ge Luo
Abstract
-methyltransferase, which mediates dimethylation of histone 3 in lysine 9 (H3K9me2), a suppressive mark for gene expression. TBC1D3 displayed an inhibitory role in G9a's histone methyltransferase activity. Treatment with G9a inhibitor markedly increased NP proliferation and promoted human cerebral organoid expansion, mimicking the effects caused by TBC1D3 up-regulation. By contrast, blockade of TBC1D3/G9a interaction to disinhibit G9a caused up-regulation of H3K9me2, suppressed NP proliferation, and impaired organoid development. Together, this study has demonstrated a mechanism underlying the role of a hominoid-specific gene in promoting cortical expansion.
Topics & Concepts
HistoneCell biologyHistone methyltransferaseMethyltransferaseProgenitor cellProgenitorNeural stem cellEpigeneticsBiologyNeuroscienceGeneGeneticsMethylationStem cellEpigenetics and DNA MethylationNeurogenesis and neuroplasticity mechanismsHistone Deacetylase Inhibitors Research