Nuclear changes in skeletal muscle extend to satellite cells in autosomal dominant Emery-Dreifuss muscular dystrophy/limb-girdle muscular dystrophy 1B

Park, Young-Eun; Hayashi, Yukiko; Goto, Kanako; Komaki, Hirofumi; Hayashi, Yuichi; Ishii, Takashi; Noguchi, S.; Nonaka, Ikuya; Nishino, Ichizo

doi:10.1016/j.nmd.2008.09.018

Cited by 52 publications

(41 citation statements)

References 18 publications

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“…A common finding among the LMNA mutations is the presence of highly distorted nuclei and marked repositioning of heterochromatin within the nucleus (Liu and Zhou, 2008; Park et al, 2009; Worman and Bonne, 2007). The nuclear lamina binds the Sun 1 and 2 proteins, which extend through the inner nuclear membrane, interact with the Nesprin-2 Giant and Nesprin 3 proteins that extend through the outer nuclear membrane, and which bind to the cytosolic actin cytoskeleton.…”

Section: Mitochondrial Explanations For Epigenetic Diseasesmentioning

confidence: 99%

“…Class I laminopathies encompasses diseases of skeletal muscle and heart, including autosomal dominant (AD)-Emery-Dreifuss muscular dystrophy (EDMD), autosomal recessive (AR)-EDMD, AD-dilated cardiomyopathy 1A, and AD-limb girdle muscular dystrophy (LGMD). EDMD and LGMD LMNA mutations present with variable degrees of muscle weakness, cardiomyopathy, and contractures (Park et al, 2009). Cardiomyopathy patients are subject to cardiac conduction defects, sudden death, and dilated cardiomyopathy, with or without skeletal muscle weakness (Perrot et al, 2009; Wolf et al, 2008).…”

Section: Mitochondrial Explanations For Epigenetic Diseasesmentioning

confidence: 99%

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Energetics, epigenetics, mitochondrial genetics

2010

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The epigenome has been hypothesized to provide the interface between the environment and the nuclear DNA (nDNA) genes. Key factors in the environment are the availability of calories and demands on the organism’s energetic capacity. Energy is funneled through glycolysis and mitochondrial oxidative phosphorylation (OXPHOS), the cellular bioenergetic systems. Since there are thousands of bioenergetic genes dispersed across the chromosomes and mitochondrial DNA (mtDNA), both cis and trans regulation of the nDNA genes is required. The bioenergetic systems convert environmental calories into ATP, acetyl-Coenzyme A (acetyl-CoA), S-adenosyl-methionine (SAM), and reduced NAD+. When calories are abundant, ATP and acetyl-CoA phosphorylate and acetylate chromatin, opening the nDNA for transcription and replication. When calories are limiting, chromatin phosphorylation and acetylation are lost and gene expression is suppressed. DNA methylaton via SAM can also be modulated by mitochondrial function. Phosphorylation and acetylation are also pivotal to regulating cellular signal transduction pathways. Therefore, bioenergetics provides the interface between the environment and the epigenome. Consistent with this conclusion, the clinical phenotypes of bioenergetic diseases are strikingly similar to those observed in epigenetic diseases (Angelman, Rett, Fragile X Syndromes, the laminopathies, cancer, etc.), and an increasing number of epigenetic diseases are being associated with mitochondrial dysfunction. This bioenergetic-epigenomic hypothesis has broad implications for the etiology, pathophysiology, and treatment of a wide range of common diseases.

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Section: Mitochondrial Explanations For Epigenetic Diseasesmentioning

confidence: 99%

Section: Mitochondrial Explanations For Epigenetic Diseasesmentioning

confidence: 99%

Energetics, epigenetics, mitochondrial genetics

2010

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“…Lamin mutations also cause obvious defects in nuclear shape and chromatin organization (Sabatelli et al 2001;Scaffidi and Misteli 2006;Shumaker et al 2006 Hakelien et al 2008;Park et al 2009b), as well as enhanced autophagic degradation of nuclei (Park et al 2009a). Further evidence for the physiological relevance of both lamins and LEM proteins in chromatin organization comes from recent genomewide studies to identify lamina-bound DNA.…”

Section: Lem-domain Proteins and Baf: Tethering Chromatin To The Nuclmentioning

confidence: 99%

Lamin-binding Proteins

Wilson¹,

Foisner²

2010

Cold Spring Harbor Perspectives in Biology

235

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A-and B-type lamins are the major intermediate filaments of the nucleus. Lamins engage in a plethora of stable and transient interactions, near the inner nuclear membrane and throughout the nucleus. Lamin-binding proteins serve an amazingly diverse range of functions. Numerous inner-membrane proteins help anchor lamin filaments to the nuclear envelope, serving as part of the nuclear "lamina" network that is essential for nuclear architecture and integrity. Certain lamin-binding proteins of the inner membrane bind partners in the outer membrane and mechanically link lamins to the cytoskeleton. Inside the nucleus, lamin-binding proteins appear to serve as the "adaptors" by which the lamina organizes chromatin, influences gene expression and epigenetic regulation, and modulates signaling pathways. Transient interactions of lamins with key components of the transcription and replication machinery may provide an additional level of regulation or support to these essential events.T he eukaryotic cell nucleus is a complex membrane-bounded organelle that houses, organizes, and regulates the genome. The nucleus is structurally organized into functional domains, one of which is the nuclear envelope (NE). The NE has two concentric membranes, named the "inner" and "outer" nuclear membranes (INM and ONM, respectively). These membranes are separated by a 30-50 nm lumen, and fuse to form holes ( pores) occupied by nuclear pore complexes (NPCs), which mediate active and passive movement of molecules between the cytoplasm and nucleoplasm (Gruenbaum et al. 2005;Stewart et al. 2007). The NE and its lumen are continuous with the endoplasmic reticulum (ER) and share many ER functions. However, the INM and ONM are also each structurally and functionally unique, because of specific enrichments for distinct integral membrane proteins Schirmer and Foisner 2007). In mammals, the INM in particular appears to be populated by over 50 different membrane proteins, most of which are uncharacterized. Among characterized INM proteins, most can bind directly to A-or B-type lamins, or both.A-and B-type lamins polymerize to form separate networks of nuclear intermediate filaments that concentrate near the INM in metazoans (Dechat et al. 2008). Many INM proteins are localized by binding directly or indirectly to lamin filaments. This network of filaments and

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“…Consistent with this, several studies have suggested that differentiation is impaired in LMNA mutant cells. [26][27][28] This differentiation defect may be the result of impaired expression result from large scale chromatin rearrangements because chromatin is displaced either towards or away from transcriptional complexes (Fig. 2).…”

confidence: 99%