Systematic characterization of chromodomain proteins reveals an H3K9me1/2 reader regulating aging in C. elegans

Xinhao Hou, Mingjing Xu, Chengming Zhu, Jianing Gao, Meili Li, Xiangyang Chen, Cheng Sun, Björn Nashan, Jianye Zang, Ying Zhou (), Shouhong Guang () and Xuezhu Feng ()
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Xinhao Hou: University of Science and Technology of China
Mingjing Xu: University of Science and Technology of China
Chengming Zhu: University of Science and Technology of China
Jianing Gao: University of Science and Technology of China
Meili Li: University of Science and Technology of China
Xiangyang Chen: University of Science and Technology of China
Cheng Sun: University of Science and Technology of China
Björn Nashan: University of Science and Technology of China
Jianye Zang: University of Science and Technology of China
Ying Zhou: University of Science and Technology of China
Shouhong Guang: University of Science and Technology of China
Xuezhu Feng: University of Science and Technology of China

Nature Communications, 2023, vol. 14, issue 1, 1-19

Abstract: Abstract The chromatin organization modifier domain (chromodomain) is an evolutionally conserved motif across eukaryotic species. The chromodomain mainly functions as a histone methyl-lysine reader to modulate gene expression, chromatin spatial conformation and genome stability. Mutations or aberrant expression of chromodomain proteins can result in cancer and other human diseases. Here, we systematically tag chromodomain proteins with green fluorescent protein (GFP) using CRISPR/Cas9 technology in C. elegans. By combining ChIP-seq analysis and imaging, we delineate a comprehensive expression and functional map of chromodomain proteins. We then conduct a candidate-based RNAi screening and identify factors that regulate the expression and subcellular localization of the chromodomain proteins. Specifically, we reveal an H3K9me1/2 reader, CEC-5, both by in vitro biochemistry and in vivo ChIP assays. MET-2, an H3K9me1/2 writer, is required for CEC-5 association with heterochromatin. Both MET-2 and CEC-5 are required for the normal lifespan of C. elegans. Furthermore, a forward genetic screening identifies a conserved Arginine124 of CEC-5’s chromodomain, which is essential for CEC-5’s association with chromatin and life span regulation. Thus, our work will serve as a reference to explore chromodomain functions and regulation in C. elegans and allow potential applications in aging-related human diseases.

Date: 2023
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DOI: 10.1038/s41467-023-36898-y

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