LncRNA Gas5 directs SUV39H2 to establish heterochromatin and maintain genome stability
Abstract
Constitutive heterochromatin, characterized by histone H3 lysine 9 trimethylation (H3K9me3), is essential for genome stability, pluripotency, and developmental fidelity. While the SUV39H histone methyltransferases catalyze H3K9me3 deposition, their locus-specific targeting mechanisms remain unclear. Here, via RNA depletion or RNA-binding affinity mutation, we establish that RNA binding is indispensable for SUV39H2 recruitment to chromatin and H3K9me3 maintenance in mouse embryonic stem cells (ESCs). Through RNA immunoprecipitation sequencing (RIP-Seq) and functional validation, we identify the long non-coding RNA Gas5 as a specific SUV39H2 interactor. Depletion of Gas5 or disruption of the SUV39H2–RNA interaction leads to the loss of self-renewal capacity of ESCs, abolishes H3K9me3 enrichment, along with profound genomic instability, mitotic errors, and γH2AX foci accumulation. These findings reveal a critical lncRNA-dependent mechanism governing the SUV39H2–H3K9me3 axis, which directly couples RNA metabolism to the preservation of pluripotency and genome integrity in stem cells.
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BibTeX
@article{liu2026lncrna,
title = {{LncRNA Gas5 directs SUV39H2 to establish heterochromatin and maintain genome stability}},
author = {Juntao Liu and Jiani Yang and Wen Ye and Dandan Zhang and Nan Su and Hong Wang and Yanping Zhang and Shaorong Gao and Lan Kang},
journal = {Protein \& Cell},
year = {2026},
month = jun,
doi = {10.1093/procel/pwag039},
url = {https://doi.org/10.1093/procel/pwag039},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - LncRNA Gas5 directs SUV39H2 to establish heterochromatin and maintain genome stability
AU - Juntao Liu
AU - Jiani Yang
AU - Wen Ye
AU - Dandan Zhang
AU - Nan Su
AU - Hong Wang
AU - Yanping Zhang
AU - Shaorong Gao
AU - Lan Kang
PY - 2026
DA - 2026/06/23
JO - Protein & Cell
DO - 10.1093/procel/pwag039
UR - https://doi.org/10.1093/procel/pwag039
AB - Constitutive heterochromatin, characterized by histone H3 lysine 9 trimethylation (H3K9me3), is essential for genome stability, pluripotency, and developmental fidelity. While the SUV39H histone methyltransferases catalyze H3K9me3 deposition, their locus-specific targeting mechanisms remain unclear. Here, via RNA depletion or RNA-binding affinity mutation, we establish that RNA binding is indispensable for SUV39H2 recruitment to chromatin and H3K9me3 maintenance in mouse embryonic stem cells (ESCs). Through RNA immunoprecipitation sequencing (RIP-Seq) and functional validation, we identify the long non-coding RNA Gas5 as a specific SUV39H2 interactor. Depletion of Gas5 or disruption of the SUV39H2–RNA interaction leads to the loss of self-renewal capacity of ESCs, abolishes H3K9me3 enrichment, along with profound genomic instability, mitotic errors, and γH2AX foci accumulation. These findings reveal a critical lncRNA-dependent mechanism governing the SUV39H2–H3K9me3 axis, which directly couples RNA metabolism to the preservation of pluripotency and genome integrity in stem cells.
SN - 1674-800X
SN - 1674-8018
ER -