Ask about this productRelated genes to: L3MBTL3 antibody
- Gene:
- L3MBTL3 NIH gene
- Name:
- L3MBTL histone methyl-lysine binding protein 3
- Previous symbol:
- -
- Synonyms:
- KIAA1798
- Chromosome:
- 6q23.1
- Locus Type:
- gene with protein product
- Date approved:
- 2003-11-26
- Date modifiied:
- 2019-01-22
Related products to: L3MBTL3 antibody
Related articles to: L3MBTL3 antibody
- Epigenetic regulation involves the coordinated interplay of diverse proteins. To systematically explore these combinations, we present COMBINE (combinatorial interaction exploration), a high-throughput platform that tests over 50,000 pairs of epigenetic effector domains up to 2,094 amino acids in length for their ability to modulate endogenous human gene transcription. COMBINE reveals diverse synergistic interactions between epigenetic protein domains, including a potent KRAB-L3MBTL3 fusion that increases the effective targeting window, enhances gene silencing in dose-limited conditions, and enables robust dual-directional CRISPR perturbation. Inducible screening shows DNA methylation modifiers are essential for epigenetic memory, with distinct combinations driving long-term repression and activation. This systematic analysis of pairwise domain interactions advances our understanding of epigenetic crosstalks and the development of next-generation epigenome editing tools. More broadly, COMBINE offers a generalizable platform to functionally characterize combinatorial biological processes at scale. - Source: PubMed
Publication date: 2026/04/24
Moon Hyungseok CHerschl Michael HSclip AlessandraTran Vincent QPawluk AprilKonermann SilvanaHsu Patrick D - BACKGROUND: To investigate the genetic causality between Human blood cell (HBC) traits and sporadic lymphangioleiomyomatosis (sLAM) by mediation joint multi-omics and eQTL Mendelian randomization analysis. METHODS: Quality control processes were followed to select eligible instrumental variables strongly associated with 35 kinds of HBC traits. Independent cohort of European ancestry with sLAM and lung function genome-wide association study (GWAS) summary statistics were used separately. We utilized a two-step MR approach to explore potential mediators and evaluate the proportion of effect mediated in the associations linking HBC trait candidates to sLAM. Finally MR analysis integrating single cell expression quantitative trait loci (sc-eQTL) from 14 immune cell types with GWAS of sLAM was conducted. RESULTS: Increased level of basophil count was positively associated with higher risk of sLAM (BASO#; OR = 3.878, 95%CI:1.137–13.221, P = 0.030). No evidences of horizontal pleiotropy were observed. The multivariable MR still demonstrated that BASO# was genetically associated with the risk of sLAM after adjustment for other blood traits in the same category(OR = 5.918, 95% CI:1.275–27.468 P = 0.023) and estradiol (OR = 3.814, 95% CI:1.130-12.874, P = 0.031) respectively. No evidence for associations between basophil traits (BASO# and basophil percentage of white cells: BASO%) and lung functions containing forced vital capacity (FVC) and forced expiratory volume in 1 s/forced vital capacity(FEV1/FVC). The estimated degree of transitional B cell absolute count mediated the effect of BASO# on sLAM by 36%, while no mediating factors, including immune cells, inflammatory proteins, VEGF-related proteins were found. We identified 12 genes in 14 immune cell types that may have a putative causal relationship with sLAM by mediating through the regulation of BASO#, such as EGFL8, PAX8, KANSL1-AS and L3MBTL3. L3MBTL3 was implicated across several immune cell types. CONCLUSIONS: For the first time, this study leverages mediation analysis and multi-omics MR integrated with sc-eQTL data to elucidate the roles of HBC traits, immune cells, inflammatory proteins, VEGF-related proteins and immune cell-specific genes in the pathogenesis of sLAM among the European populations. - Source: PubMed
Publication date: 2026/01/27
Liu TianshuCai Yiting - BACKGROUND: Hand grip strength is a crucial indicator of muscle strength and quality. Yet, there remain significant knowledge gaps in our understanding of the genetic factors that influence hand grip strength and its impact on digestive disorders. METHODS: This study employed data from the UK Biobank, comprising 405,394 individuals of European ancestry, who underwent assessments of both left- and right- hand grip strength at baseline. We calculated the relative hand grip strength (RHGS), defined as the average hand grip strength adjusted for body mass index (BMI). Subsequently, we performed genome-wide association study (GWAS) to identify RHGS-linked variants and genes. We evaluated RHGS’s impact on digestive disorders using linkage disequilibrium score regression (LDSC), Mendelian randomization (MR), Polygenic risk score (PRS), regression models, and interaction analyses. RESULTS: GWAS of 405,394 Europeans identified 1,111 independent SNPs across 226 autosomal loci and 407 genes associated with RHGS. TWAS with skeletal-muscle eQTLs prioritized genes, including L3MBTL3, CEP192 and NUCKS1, highly expressed in type I/II myocytes and mesenchymal cells. LDSC revealed significant negative genetic correlations between RHGS and abdominal hernia (rg = -0.121, p = 5.00 × 10⁻⁴), diaphragmatic hernia (rg = -0.155, p = 6.33 × 10⁻⁶) and diverticular intestine (rg = -0.141, p = 3.85 × 10⁻¹⁰). MR indicated that one-unit higher genetically predicted RHGS reduced odds of diaphragmatic hernia (OR = 0.45, 95% CI 0.25–0.82), diverticular intestine (OR = 0.42, 0.26–0.66), NAFLD (OR = 0.49, 0.29–0.83) and peptic ulcer (OR = 0.54, 0.31–0.97). Each standard-deviation increase in RHGS PRS was associated with lower risks of abdominal hernia (OR = 0.98), diaphragmatic hernia (OR = 0.96) and diverticular intestine (OR = 0.98) after full adjustment. Gene-environment analyses showed diabetes, hyperlipidemia and smoking attenuated the protective effects from elevated RHGS, whereas cardioprotective diet and higher fiber intake showed synergistic protection on abdominal hernia, diaphragmatic hernia and diverticular intestine. CONCLUSION: We identified multiple RHGS-associated loci enriched in skeletal muscle. Genetically high RHGS inversely correlated with risks of abdominal hernia, diaphragmatic hernia and diverticular intestine. RHGS polygenic risk score enables risk stratification, and its effects are modulated by diet and common comorbidities. - Source: PubMed
Publication date: 2026/01/27
Jiang PanFang YanfeiLiu ZhengyeDu HanzeBai XiaoyinChen HaotianMi Jiarui - Sarcopenia and frailty are complex geriatric syndromes influenced by a combination of genetic and environmental factors. Recent studies suggest that specific genetic variants, DNA methylation patterns and shortened telomeres are associated with age-related diseases and might contribute to the development of both sarcopenia and frailty. In this study, we investigated the contribution of multi-omics data to sarcopenia, frailty, lean mass index (LMI) and handgrip strength in an elderly Lithuanian population. A total of 204 participants (age 82.2 ± 7.6 years) were included, comprising 122 individuals diagnosed with sarcopenia and/or frailty and 82 healthy, community-dwelling older adults. The results showed that LMI was associated with various health and lifestyle factors. Two genetic variants, CLIC5 rs75652203 and GHITM rs17102732, were found to be significantly associated with handgrip strength at the genome-wide level. Additionally, 12 polymorphisms previously linked to sarcopenia were replicated in relationship to LMI: BOK rs76993203, VAMP5 rs1374370, TMEM18 rs12714414, SFMBT1 rs36033494, BANK1 rs13136118, TET2 rs2647239, FOXO3 rs9384679, L3MBTL3 rs13209574, ZFAT rs13267329, CEP57 rs35793328, PCGF2 rs1985352 and MC4R rs66922415. Furthermore, several genes, many of which are involved in immune system processes, were significantly enriched with differentially methylated sites associated with LMI. Shorter telomeres were also associated with both sarcopenia and frailty. Notably, a significant relationship was observed between telomere length and methylation levels in genes related to lifestyle traits and the risk of developing these conditions. These findings provide new insights into the biological mechanisms underlying sarcopenia and frailty, underscoring the important roles of genetic and epigenetic factors in their pathogenesis among older adults. - Source: PubMed
Publication date: 2025/09/27
Ginevičienė ValentinaPranckevičienė ErinijaUrnikytė AlinaJurkūnaitė LauraGutauskaitė KristijonaDadelienė RūtaKilaitė JustinaJamontaitė Ieva EglėMastavičiūtė AstaAhmetov Ildus IAlekna Vidmantas - Transcription factors orchestrate gene expression through a myriad of complex mechanisms, encompassing collaborations with other transcription factors and the formation of multimeric complexes. The chromatin-binding protein SAMD1 [sterile alpha motif (SAM) domain-containing protein 1] binds to unmethylated CpG-rich DNA utilizing its N-terminal winged-helix (WH) domain. Additionally, its C-terminal SAM domain, which mediates interactions with itself and with L3MBTL3, is crucial for chromatin binding. The precise role of the SAM domain in this process remains unclear. Using structural analyses, we elucidated the distinct homopolymerization modes within the SAM domains of L3MBTL3 and SAMD1, alongside their heterodimerization architecture. Interestingly, SAMD1 necessitates not only the WH and SAM domain but also a proline/alanine-rich intrinsically disordered region (IDR) for efficient chromatin binding. The IDR is essential for the ability of SAMD1 to form large polymers, with its functionality determined by integrity rather than the specific sequence. Mutagenesis studies underscore the critical role of arginines within the IDR for polymerization, chromatin binding, and the biological function of SAMD1. These findings propose a model in which structured and unstructured regions of SAMD1 cooperate in a coordinated fashion to facilitate chromatin binding. This work provides new insights into the diverse mechanisms transcription factors employ to interact with chromatin and regulate gene expression. - Source: PubMed
Geller MerleCao YinghuaSimon ClaraStielow BastianXu JingfeiWei PengshuaiNist AndreaRohner IrisJeude Lea MarieHuber TheresaStiewe ThorstenWang ZhanxinLiefke Robert