Ask about this productRelated genes to: SUV39H2 antibody
- Gene:
- SUV39H2 NIH gene
- Name:
- suppressor of variegation 3-9 homolog 2
- Previous symbol:
- -
- Synonyms:
- FLJ23414, KMT1B
- Chromosome:
- 10p13
- Locus Type:
- gene with protein product
- Date approved:
- 2003-11-11
- Date modifiied:
- 2015-12-04
Related products to: SUV39H2 antibody
Related articles to: SUV39H2 antibody
- Triple-negative breast cancer (TNBC) exhibits iron homeostasis that supports tumor growth and proliferation, yet the regulatory mechanisms controlling iron flux remain poorly defined. Here, we identify a ferritinophagic cargo receptor NCOA4 as a novel substrate of the lysine methyltransferase SUV39H2, uncovering a previously unrecognized mechanism that regulates ferritinophagy and ferroptosis. SUV39H2 directly binds and mono-methylates NCOA4 at lysine 356, a modification that reduces NCOA4 stability. Mechanistically, K356 methylation enhances NCOA4 interaction with the E3 ligase HERC2, promoting its ubiquitination and proteasomal degradation. This degradation increases FTH1 stability, suppresses ferritinophagic flux, limits iron release, maintains the high-risk iron homeostasis and ferroptosis resistance, ultimately promoting tumor proliferation and chemoresistance. Conversely, genetic or pharmacologic inhibition of SUV39H2 (OTS186935) inhibit NCOA4 methylation, stabilizes NCOA4 protein, enhances ferritinophagy, and triggers ferroptosis. Furthermore, SUV39H2 inhibition sensitizes TNBC cells to chemotherapy in vitro and in vivo, indicating OTS186935 treatment is a feasible therapeutic strategy. Collectively, the SUV39H2-NCOA4-HERC2 axis as a critical regulatory pathway in iron metabolism and ferroptosis, and highlight inhibition of NCOA4 K356 methylation as a promising therapeutic target in TNBC.The mechanistic scheme of SUV39H2 depletion to facilitate ferroptosis in TNBC. A SUV39H2 binds and methylates NCOA4, which enhanced the interaction between NCOA4 and the E3 ubiquitin ligase HERC2, leading to NCOA4 ubiquitination and proteasomal degradation. As a result, iron metabolism was reprogramed via enhancing ferritinophagy, leading to an increase in the level of iron, ultimately triggering ferroptosis. B Cell-state transitions induced by SUV39H2. - Source: PubMed
Publication date: 2026/07/16
Liu LingxiaPei XinyunLi DingHuo YingWang ZhaotingZhang QiuYue YuanDeng BaoYu MinminXu TongZhong LeiRuan XianhuiLi Xichuan - 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. - Source: PubMed
Publication date: 2026/06/23
Liu JuntaoYang JianiYe WenZhang DandanSu NanWang HongZhang YanpingGao ShaorongKang Lan - Despite the expression of multiple transcript isoforms from a gene, conventional gene expression analyses assume that a single transcript is expressed from each gene. We analyzed the transcript isoforms expressed in gonadotropin-induced mouse mural and cumulus granulosa cells (mGCs and cGCs) isolated from antral follicles to elucidate the potential mechanism of differentiation. Considering that either a single transcript or multiple isoforms are expressed from genes, we identified differential expression of about 70% of transcripts between mGCs and cGCs. Although the differential expressions were similar, the single-transcript-wise differentially expressed genes did not correlate with their corresponding differentially expressed transcript isoforms. We identified transcript isoforms of key transcriptional regulators in ovaries, including Chd1, Ezh2, Kdm5a/5b, Gata4, Esr2, Fos, Myc, and Ybx1, that were not identified in single-transcript-based analyses. Further analysis revealed a transcript switch in more than 30% of the differentially expressed isoforms. While one or more transcript isoforms of Cebpa, Dnmt3a, Pgr, Rest, Runx1, and Sirt1 were switched off, those of Brd7, Chd1, Med21, Nfkbia, Rbm39, Suv39h2, Tcf12, Xist, and Ybx3 were switched on in cGCs. Interestingly, several genes, including Dab2, Ezh2, Gata4, Gnas, Gtf2i, Klf10, Setdb1, and Sp3, exhibited at least one isoform that was switched off and another that was switched on in cGCs. Transcript switching was primarily due to alternative splicing, followed by alternative transcription start sites and polyadenylation sites. We also identified differential expression of the potential regulators of such transcript switching in cGCs. Our results suggest that transcript switching may play an important role in mural and cumulus granulosa differentiation, a key insight that would remain unknown without mRNA isoform analysis. - Source: PubMed
Publication date: 2026/05/23
Shila SharminPei Grace JBahadursingh ElizabethPeramsetty NikiDahiya VineshMarsh Courtney AThiyagarajan RamkumarZhang MeijiaFields Patrick ERumi M A Karim - Liver and lymph node endothelial cell C-type lectin (LSECtin) loss in liver sinusoidal endothelial cells (LSECs) during cirrhosis favors hepatic pro-inflammatory T-cell infiltration. We characterize histone protein post-translational modifications and DNA methylation in LSECs that may control LSECtin expression and evaluate methyltransferase inhibitors' capacity to retrieve LSECtin. - Source: PubMed
Publication date: 2026/05/22
Ángel-Gomis EnriqueGómez-Hurtado IsabelFernández-Barrena Maite GJuanola OriolMartínez-López SebastiánBoix PaulaÁvila Matías ACaparrós EstherFrancés Rubén - Histone H3K9me3 silences repetitive elements and represses non-lineage genes during early development, but its role in organogenesis is understudied. Here, we show that H3K9me3 deposition is dynamic during epidermis morphogenesis and essential for lineage diversification. We ablate Suv39h1, Suv39h2, and Setdb1 histone methyltransferases, in the embryonic mouse epidermis, to induce H3K9me3 loss. This causes complete failure of keratinocyte differentiation, skin barrier formation, hair follicle development, and Merkel cell specification. Single-cell transcriptomics reveals aberrant cell fates with mixed epidermal subtype identities and dysregulated non-lineage and lineage-specific transcription programs. Affected pathways include differentiation, metabolism, cell cycle, cytoskeletal organization, and extracellular matrix. H3K9me3 primarily restricts RNA Pol II transcription initiation at key developmental promoters and enhancers and has minimal direct effect on promoter-proximal pause release. We uncover a cooperative and indispensable role for Suv39h1, Suv39h2, and Setdb1 in gene expression control of epidermal morphogenesis, establishing H3K9me3 as a critical developmental determinant of skin organogenesis. - Source: PubMed
Publication date: 2026/05/15
Bai Chris KeChovatiya GopalPollack Emily JanineLiao Yu-ChingKim Ashley NayeonTumbar Tudorita