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Integrative high-throughput enhancer surveying and functional verification divulges a YY2-condensed regulatory axis conferring risk for osteoporosis

Cell Genom. 2024-03; 
Xiao-Feng Chen, Yuan-Yuan Duan, Ying-Ying Jia, Qian-Hua Dong, Wei Shi, Yan Zhang, Shan-Shan Dong, Meng Li, Zhongbo Liu, Fei Chen, Xiao-Ting Huang, Ruo-Han Hao, Dong-Li Zhu, Rui-Hua Jing, Yan Guo, Tie-Lin Yang
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摘要

The precise roles of chromatin organization at osteoporosis risk loci remain largely elusive. Here, we combined chromatin interaction conformation (Hi-C) profiling and self-transcribing active regulatory region sequencing (STARR-seq) to qualify enhancer activities of prioritized osteoporosis-associated single-nucleotide polymorphisms (SNPs). We identified 319 SNPs with biased allelic enhancer activity effect (baaSNPs) that linked to hundreds of candidate target genes through chromatin interactions across 146 loci. Functional characterizations revealed active epigenetic enrichment for baaSNPs and prevailing osteoporosis-relevant regulatory roles for their chromatin interaction genes. Further motif enrichment and... More

关键词

Hi-C; PAPSS2; STARR-seq; YY2; chromatin interaction; enhancer; genetic regulatory network; osteoblast differentiation; osteoporosis; transcription factor.