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The LMNA gene encodes the A-type lamins, which are intermediate filament proteins that are major
components of the nuclear lamina (Gruenbaum et al. 2000; Burke and Stewart 2002; Holaska et al. 2002).
The nuclear lamina has both structural and functional roles in multiple nuclear processes, including
DNA replication and regulation of gene expression. Lamin A/C expression is typically expressed
specifically in differentiated cell types (Rober et al. 1989). It has been suggested, although not
formally demonstrated, that upregulation of lamin A/C may restrict the differentiative capacity of
cells during development (Stewart and Burke 1987). The Kennedy Lab hypothesizes that lamin A/C
plays a direct role in differentiation by stabilizing tissue specific transcription factors to limit
proliferation and maintain the program of gene expression of the differentiated state. If this
hypothesis is correct, it could explain how the disruption of lamin A/C results in degeneration of
differentiated tissues, such as that seen in numerous human diseases known as the laminopathies.
The Kennedy Lab is currently developing an in vitro differentiation system, using embryonic stem
cells as a progenitor population, in order to ask whether lamin A/C regulates gene expression.
Dr. Smith assayed the available immunological reagents for detecting mouse lamin A/C by
immunofluorescence and for isolating lamin A/C-associating proteins and genes by chromatin
immunoprecipitation. Dr. Smith’s main objective for the next few months is to determine what
fraction of genes that are expressed in a tissue-specific manner (in embryonic stem cells that
have been differentiated into myotubes in vitro) are associated with lamin A/C in the nucleus
using chromatin immunopreciptiation and microarray analysis. The Kennedy Lab is in the process
of establishing the chromatin immunoprecipitation technique in our laboratory and have contacted
the microarray facility to assess our options for the analysis. The Kennedy Lab hopes to have the
chromatin immunoprecipitated material ready for microarray analysis by late spring.
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