Volume 117, Issue 5, September 2025, 111085Author links open overlay panel, , , , , , , Highlights•

This study first reveals 5hmC enrichment in lncRNA genes across diverse human tissues.

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The study uncovers strong correlations between 5hmC-modified lncRNA genes and tissue-specific expression.

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Bioinformatics analysis reveals functional roles of 5hmC-modified lncRNA genes in tissue-specific processes.

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This study provides a basis for disease diagnosis and therapy based on 5hmC-modified lncRNA genes.

Abstract

This study investigates the role of 5-hydroxymethylcytosine (5hmC) in long non-coding RNA (lncRNA) genes across diverse human tissues, a topic that has remained underexplored despite previous studies highlighting its contributions to development and tissue specificity. We analyzed 15 human tissue samples using 5hmC sequencing (5hmC-seq) to map the distribution of 5hmC across the genome. Specific enrichment of 5hmC was observed in lncRNA genes, particularly those with tissue-specific expression patterns. Bioinformatics analysis revealed strong correlations between the tissue-specific 5hmC-modified lncRNA genes and their respective functional roles in different tissues. Additionally, pathway enrichment and functional annotation analyses of target genes of key 5hmC-modified lncRNA genes provided further insights into their potential involvement in tissue-specific processes. These findings underscore the significant role of 5hmC modifications in regulating the function of lncRNA genes linked to tissue specificity, offering a foundation for future research on the clinical implications of lncRNA 5hmC modifications.

Keywords

5hmC

Long non-coding RNA genes

Tissue specificity

Genomic distribution

Functional annotation

Data availabilityThe raw sequence data reported in this paper have been deposited in the Genome Sequence Archive (PRJCA025053) that are publicly accessible at https://ngdc.cncb.ac.cn/gsa.

© 2025 The Authors. Published by Elsevier Inc.