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
- DNA packaging into heterochromatin is a fundamental mechanism of transcriptional silencing, yet its role in regulating neural progenitor behavior during brain development remains poorly understood. Trimethylation of histone H3 lysine 9 (H3K9me3), catalyzed by the methyltransferases SETDB1, SUV39H1, and SUV39H2, is a defining feature of heterochromatin, but functional redundancy among these enzymes has obscured their developmental roles. Here, we generated a cortex-specific triple knockout mouse model lacking Setdb1, Suv39h1, and Suv39h2 to directly interrogate H3K9me3 function during corticogenesis. Combined loss of H3K9 methyltransferases caused genome-wide depletion of H3K9me3, disruption of neural progenitor cell-cycle progression, and impaired cortical neurogenesis, resulting in microcephaly. H3K9 methyltransferases preserve neural progenitor identity and function by silencing clustered protocadherins, meiosis-associated genes, and a cell-cycle restraint program through H3K9me3 deposition. Loss of H3K9me3 promoted local chromatin opening and increased transcription factor occupancy, enabling transposable elements to acquire cryptic enhancer activity and modulate proximal gene expression. Together, these findings establish H3K9me3 heterochromatin as an active regulator of neural progenitor dynamics and lineage fidelity, revealing a central epigenetic mechanism that restricts aberrant transcriptional programs to ensure cortical growth. - Source: PubMed
Publication date: 2026/09/08
Warren SophieHemmerich ChrisPodicheti RamBaizabal José-Manuel - The spatial organization of the genome within the nucleus is a critical determinant of gene regulation, genome stability, and cellular identity. Disruption of nuclear architecture is increasingly recognized as a hallmark of cancer, contributing to transcriptional dysregulation, epigenetic reprogramming, and metastatic progression. Nuclear lamins, as key structural components of the nuclear envelope, play central roles in maintaining nuclear integrity and organizing chromatin through lamina-associated domains that are enriched in transcriptionally repressive states. Emerging pan-cancer studies reveal widespread dysregulation of lamin genes, with context-dependent roles in tumor suppression and oncogenesis. Alterations in lamin expression not only impact chromatin organization and gene expression but also influence nuclear mechanics, thereby facilitating invasion and metastasis. Increasing evidence suggests that epigenetic mechanisms tightly regulate lamin expression and function, linking chromatin state to nuclear structure. This interplay between epigenetic regulation and nuclear architecture drives large-scale genome reorganization and transcriptional plasticity in cancer. This review discusses the role of nuclear architecture in tumorigenesis, the contribution of lamins to chromatin organization, and the emerging epigenetic control of lamins in cancer progression and metastasis. - Source: PubMed
Publication date: 2026/08/17
Kundu Subhadip - 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