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LMNA encodes nuclear Lamin A/C that tethers lamina-associated domains (LADs) to the nuclear periphery. Mutations in LMNA cause degenerative disorders including the premature aging disorder Hutchinson-Gilford progeria, but the mechanisms are unknown. We report that Ser22-phosphorylated (pS22) Lamin A/C was localized to the nuclear interior in human fibroblasts throughout the cell cycle. pS22-Lamin A/C interacted with a subset of putative active enhancers, not LADs, at locations co-bound by the transcriptional activator c-Jun. In progeria-patient fibroblasts, a subset of pS22-Lamin A/C-binding sites were lost, whereas new pS22-Lamin A/C-binding sites emerged in normally quiescent loci. New pS22-Lamin A/C binding was accompanied by increased histone acetylation, increased c-Jun binding, and upregulation of nearby genes implicated in progeria pathophysiology. These results suggest that Lamin A/C regulates gene expression by enhancer binding. Disruption of the gene regulatory rather than LAD tethering function of Lamin A/C may underlie the pathogenesis of disorders caused by LMNA mutations.
This article was published in the following journal.
Name: Developmental cell
Lamin proteins not only form the nuclear lamina, but some are also found in the nuclear interior. In this issue of Developmental Cell, Ikegami et al. describe that phosphorylated Lamin C in the nucle...
Lamin proteins are major constituents of the nuclear lamina. They are required for fundamental nuclear activities, as evidenced by the large number of laminopathies. Mutations in the human lamin A/C g...
Nuclear actin plays a critical role in mediating mesenchymal stem cell (MSC) fate commitment. In marrow derived MSCs, the principal diaphanous-related formin Diaph3 (mDia2) is present in the nucleus a...
Mutations in LRRK2 cause autosomal dominant and sporadic Parkinson's disease but the mechanisms involved in LRRK2 toxicity in PD are yet to be fully understood. We found that LRRK2 translocates to the...
Apoptosis of vascular smooth muscle cells (VSMCs) influenced by abnormal cyclic stretch is crucial for vascular remodeling during hypertension. Lamin A/C, a nuclear envelope protein, is mechano-respon...
Progerias are rare "premature aging" diseases in which children die of severe atherosclerosis leading to strokes and heart attacks. It is a multisystem disease with objective clinical mar...
This study seeks to discover clinically useful tests to improve the diagnosis of a rare and serious heart muscle disease caused by mutations in a gene called 'Lamin'. Patients born with l...
The pupose of the study is to compare effects of treatment of patients acutely admitted to a Psychiatric Intensive Care Unit (PICU) with either a sparsely decorated interior or interior de...
This is a randomized, double-blind, placebo-controlled study in patients with dilated cardiomyopathy (DCM) due to a gene encoding the lamin A/C protein (LMNA) mutation. The study will furt...
The purpose of the study is to compare efficacy of DCVAC/LuCa + chemotherapy +/- immune enhancers vs. chemotherapy alone in patients with stage IV NSCLC, as measured by progression free su...
The residual framework structure of the CELL NUCLEUS that maintains many of the overall architectural features of the cell nucleus including the nuclear lamina with NUCLEAR PORE complex structures, residual CELL NUCLEOLI and an extensive fibrogranular structure in the nuclear interior. (Advan. Enzyme Regul. 2002; 42:39-52)
A subclass of developmentally regulated lamins having a neutral isoelectric point. They are found to disassociate from nuclear membranes during mitosis.
A subclass of ubiquitously-expressed lamins having an acidic isoelectric point. They are found to remain bound to nuclear membranes during mitosis.
Various material objects and items in the home. It includes temporary or permanent machinery and appliances. It does not include furniture or interior furnishings (FURNITURE see INTERIOR DESIGN AND FURNISHINGS; INTERIOR FURNISHINGS see INTERIOR DESIGN AND FURNISHINGS).
An enzyme that catalyzes the degradation of GLYCOGEN in animals by releasing glucose-1-phosphate from the terminal alpha-1,4-glycosidic bond. This enzyme exists in two forms: an active phosphorylated form ( PHOSPHORYLASE A) and an inactive un-phosphorylated form (PHOSPHORYLASE B). Both a and b forms of phosphorylase exist as homodimers. In mammals, the major isozymes of glycogen phosphorylase are found in muscle, liver and brain tissue.
The process of gene expression is used by eukaryotes, prokaryotes, and viruses to generate the macromolecular machinery for life. Steps in the gene expression process may be modulated, including the transcription, RNA splicing, translation, and post-tran...