Hutchinson-Gilford progeria syndrome through the lens of transcription

Aging Cell. 2013 Aug;12(4):533-43. doi: 10.1111/acel.12070. Epub 2013 Apr 19.

Abstract

Lamins are nuclear intermediate filaments. In addition to their structural roles, they are implicated in basic nuclear functions such as chromatin organization, DNA replication, transcription, DNA repair, and cell-cycle progression. Mutations in human LMNA gene cause several diseases termed laminopathies. One of the laminopathic diseases is Hutchinson-Gilford progeria syndrome (HGPS), which is caused by a spontaneous mutation and characterized by premature aging. HGPS phenotypes share certain similarities with several apparently comparable medical conditions, such as aging and atherosclerosis, with the conspicuous absence of neuronal degeneration and cancer rarity during the short lifespan of the patients. Cell lines from HGPS patients are characterized by multiple nuclear defects, which include abnormal morphology, altered histone modification patterns, and increased DNA damage. These cell lines provide insight into the molecular pathways including senescence that require lamins A and B1. Here, we review recent data on HGPS phenotypes through the lens of transcriptional deregulation caused by lack of functional lamin A, progerin accumulation, and lamin B1 silencing.

Keywords: Hutchinson-Gilford progeria syndrome; LMNA; aging; lamin A; lamin B1; nuclear lamina; progerin; transcription.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adult Stem Cells / metabolism
  • Adult Stem Cells / pathology
  • Cell Nucleus / genetics
  • Cell Nucleus / metabolism
  • Chromatin Assembly and Disassembly
  • DNA Repair
  • Gene Silencing
  • Humans
  • Lamin Type A / genetics
  • Lamin Type A / metabolism*
  • Lamin Type B / genetics
  • Lamin Type B / metabolism*
  • Mechanotransduction, Cellular
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Phenotype
  • Progeria / genetics*
  • Progeria / metabolism
  • Progeria / pathology
  • Protein Precursors / genetics
  • Protein Precursors / metabolism*
  • Telomere / genetics
  • Telomere / metabolism
  • Transcription, Genetic*

Substances

  • LMNA protein, human
  • Lamin Type A
  • Lamin Type B
  • Nuclear Proteins
  • Protein Precursors
  • lamin B1
  • prelamin A