Gene expression, chromosome position and lamin A/C mutations

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

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
JournalNucleus
Volume2
Issue number3
DOIs
StatePublished - Jan 1 2011

Keywords

  • Chromosome territory
  • Gene expression
  • Linc complex
  • Lmna

ASJC Scopus subject areas

  • Cell Biology

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