Gene expression, chromosome position and lamin A/C mutations

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32 Scopus citations


The nuclear lamina is increasinglybeing appreciated for its epigeneticrole in regulating gene expression.The nuclear lamina underlies the innernuclear membrane and, in post mitoticcells, is composed of a latticework primarilyformed by the intermediate filamentprotein, lamin A/C. Although not welldefined, lamin-associated domains havebeen described, and these domains aredetermined by DNA sequence and chromatinconformation. Lamin-associateddomains are positioned to mediate theinteraction with the nuclear membrane,where they contribute to transcriptionalregulation. Although lamin-associateddomains are primarily considered tobe repressive in nature, those nearer tonuclear pores may actually promote transcription.Mutations in LMNA, the geneencoding lamins A and C, are a relativelycommon cause of inherited cardiomyopathy.As substantial data supports a role forthe lamina in its interaction with chromatinand gene regulation, we examined therole of a genetically disrupted lamina andthe consequences thereof. A dominantLMNA mutation, E161K, that causesinherited cardiomyopathy was studied.Gene expression changes were profiled ina human cardiomyopathic E161K heart,and it was found that chromosome 13had a high percentage of misexpressedgenes. Chromosome 13 was also found tobe less tightly associated with the nuclearmembrane in E161K mutant cells,thereby linking abnormal gene expressionand intranuclear position. Theseand other studies support a role for thenuclear membrane as an active regulatorof gene expression and provide additionalsupport that disrupting this regulation isa mechanism of human disease.

Original languageEnglish (US)
Pages (from-to)162-167
Number of pages6
Issue number3
StatePublished - 2011


  • Chromosome territory
  • Gene expression
  • Linc complex
  • Lmna

ASJC Scopus subject areas

  • Cell Biology

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