Lysine methyltransferase 2D regulates muscle fiber size and muscle cell differentiation

Wright, Alec M.; Hall, A. N.; Daly, Tara; Fontelonga, Tatiana; Potter, Sarah; Schafer, Caitlin; Lindsley, Andrew; Hung, Christina; Bodamer, Olaf A.; Gussoni, Emanuela

doi:10.1096/fj.202100823r

Cited by 8 publications

(4 citation statements)

References 44 publications

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“…Muscular hypotonia is highly prevalent (51–98%) and may lead to long-term sequelae including developmental delays and oromotor dysfunction [ 66 ]. Emerging evidence suggests that hypotonia may be due to a primary defect in skeletal muscle [ 67 ]. Dysarthria is not uncommon (10–26%) and may be underestimated [ 68 ].…”

Section: Resultsmentioning

confidence: 99%

From Genotype to Phenotype—A Review of Kabuki Syndrome

Barry

Tsaparlis

Hoffman

et al. 2022

Genes

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Kabuki syndrome (KS) is a rare neuro-developmental disorder caused by variants in genes of histone modification, including KMT2D and KDM6A. This review assesses our current understanding of KS, which was originally named Niikawa–Kuroki syndrome, and aims to guide surveillance and medical care of affected individuals as well as identify gaps in knowledge and unmet patient needs. Ovid MEDLINE and EMBASE databases were searched from 1981 to 2021 to identify reports related to genotype and systems-based phenotype characterization of KS. A total of 2418 articles were retrieved, and 152 were included in this review, representing a total of 1369 individuals with KS. Genotype, phenotype, and the developmental and behavioral profile of KS are reviewed. There is a continuous clinical phenotype spectrum associated with KS with notable variability between affected individuals and an emerging genotype–phenotype correlation. The observed clinical variability may be attributable to differences in genotypes and/or unknown genetic and epigenetic factors. Clinical management is symptom oriented, fragmented, and lacks established clinical care standards. Additional research should focus on enhancing understanding of the burden of illness, the impact on quality of life, the adult phenotype, life expectancy and development of standard-of-care guidelines.

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Section: Resultsmentioning

confidence: 99%

From Genotype to Phenotype—A Review of Kabuki Syndrome

Barry

Tsaparlis

Hoffman

et al. 2022

Genes

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show abstract

“…Kmt2d is expressed in the developing mouse calvarial osteoblasts, epithelia, and neural tissues [40]. Moreover, the heterozygous loss of Kmt2d impairs the neuromuscular junction, muscle cell differentiation, and myofiber regeneration [2]. In addition, a growing body of research indicates that defects in neural crest development are a major cause of KS [41,42].…”

Section: Discussionmentioning

confidence: 99%

“…Kabuki syndrome (KS) is a rare genetic disorder caused by mutations in the histone modifier genes encoding histone H3 lysine 4 methyltransferase (KMT2D) and histone H3 lysine 27 demethylase (KDM6A) (OMIM: #147920 and #300867) [1,2]. The main clinical manifestations of KS include dysmorphic facial features, skeletal abnormalities, intellectual disability, hearing loss, and retarded postnatal growth.…”

Section: Introductionmentioning

confidence: 99%

Single-Cell Transcriptome Analysis Defines Expression of Kabuki Syndrome-Associated KMT2D Targets and Interacting Partners

Enkhmandakh

Robson

Joshi

et al. 2022

Stem Cells International

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Objectives. Kabuki syndrome (KS) is a rare genetic disorder characterized by developmental delay, retarded growth, and cardiac, gastrointestinal, neurocognitive, renal, craniofacial, dental, and skeletal defects. KS is caused by mutations in the genes encoding histone H3 lysine 4 methyltransferase (KMT2D) and histone H3 lysine 27 demethylase (KDM6A), which are core components of the complex of proteins associated with histone H3 lysine 4 methyltransferase SET1 (SET1/COMPASS). Using single-cell RNA data, we examined the expression profiles of Kmt2d and Kdm6a in the mouse dental pulp. In the incisor pulp, Kmt2d and Kdm6a colocalize with other genes of the SET1/COMPASS complex comprised of the WD-repeat protein 5 gene (Wdr5), the retinoblastoma-binding protein 5 gene (Rbbp5), absent, small, and homeotic 2-like protein-encoding gene (Ash2l), nuclear receptor cofactor 6 gene (Ncoa6), and Pax-interacting protein 1 gene (Ptip1). In addition, we found that Kmt2d and Kdm6a coexpress with the downstream target genes of the Wingless and Integrated (WNT) and sonic hedgehog signaling pathways in mesenchymal stem/stromal cells (MSCs) at different stages of osteogenic differentiation. Taken together, our results suggest an essential role of KMT2D and KDK6A in directing lineage-specific gene expression during differentiation of MSCs.

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“…Histone methyltransferase complexes are widely involved in the regulation of muscle development [ 75 , 76 ]. Mutations in KDM6A and KMT2D can reduce myocyte differentiation in vitro and damage muscle fiber regeneration in vivo [ 77 ].…”

Section: Discussionmentioning

confidence: 99%

Comparative Transcriptomic Analysis of mRNAs, miRNAs and lncRNAs in the Longissimus dorsi Muscles between Fat-Type and Lean-Type Pigs

Zhang

Wang

et al. 2022

Biomolecules

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In pigs, meat quality and production are two important traits affecting the pig industry and human health. Compared to lean-type pigs, fat-type pigs contain higher intramuscular fat (IMF) contents, better taste and nutritional value. To uncover genetic factors controlling differences related to IMF in pig muscle, we performed RNA-seq analysis on the transcriptomes of the longissimus dorsi (LD) muscle of Laiwu pigs (LW, fat-type pigs) and commercial Duroc × Landrace × Yorkshire pigs (DLY, lean-type pigs) at 150 d to compare the expression profiles of mRNA, miRNA and lncRNA. A total of 225 mRNAs, 12 miRNAs and 57 lncRNAs were found to be differentially expressed at the criteria of |log2(foldchange)| > 1 and q < 0.05. The mRNA expression of LDHB was significantly higher in the LD muscle of LW compared to DLY pigs with log2(foldchange) being 9.66. Using protein interaction prediction method, we identified more interactions of estrogen-related receptor alpha (ESRRA) associated with upregulated mRNAs, whereas versican (VCAN) and proenkephalin (PENK) were associated with downregulated mRNAs in LW pigs. Integrated analysis on differentially expressed (DE) mRNAs and miRNAs in the LD muscle between LW and DLY pigs revealed two network modules: between five upregulated mRNA genes (GALNT15, FKBP5, PPARGC1A, LOC110258214 and LOC110258215) and six downregulated miRNA genes (ssc-let-7a, ssc-miR190-3p, ssc-miR356-5p, ssc-miR573-5p, ssc-miR204-5p and ssc-miR-10383), and between three downregulated DE mRNA genes (IFRD1, LOC110258600 and LOC102158401) and six upregulated DE miRNA genes (ssc-miR1379-3p, ssc-miR1379-5p, ssc-miR397-5p, ssc-miR1358-5p, ssc-miR299-5p and ssc-miR1156-5p) in LW pigs. Based on the mRNA and ncRNA binding site targeting database, we constructed a regulatory network with miRNA as the center and mRNA and lncRNA as the target genes, including GALNT15/ssc-let-7a/LOC100523888, IFRD1/ssc-miR1379-5p/CD99, etc., forming a ceRNA network in the LD muscles that are differentially expressed between LW and DLY pigs. Collectively, these data may provide resources for further investigation of molecular mechanisms underlying differences in meat traits between lean- and fat-type pigs.

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Lysine methyltransferase 2D regulates muscle fiber size and muscle cell differentiation

Abstract: This is an open access article under the terms of the Creat ive Commo ns Attri butio n-NonCo mmerc ial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Cited by 8 publications

References 44 publications

From Genotype to Phenotype—A Review of Kabuki Syndrome

From Genotype to Phenotype—A Review of Kabuki Syndrome

Single-Cell Transcriptome Analysis Defines Expression of Kabuki Syndrome-Associated KMT2D Targets and Interacting Partners

Comparative Transcriptomic Analysis of mRNAs, miRNAs and lncRNAs in the Longissimus dorsi Muscles between Fat-Type and Lean-Type Pigs

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