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Folding of the
chromatin fiber into higher order secondary and tertiary chromatin
structures (shown below) is intimately linked to nuclear functions
involving DNA metabolism, e.g., transcription, replication. The focus
of our research falls into three areas:
1) the structural
dynamics of chromatin fibers, emphasizing the functions of the core and
linker histones, (2) the structure of MeCP2 and its influence on
 chromatin
fiber architecture, including the molecular links between MeCP2 and Rett Syndrome, and (3) intrinsically disordered nuclear proteins. We
study these topics from a biochemical and biophysical perspective.
Experimentally, the lab makes extensive use of targeted mutagenesis,
protein expression and purification, and solution biochemical and
biophysical techniques (e.g., analytical ultracentrifugation, gel
electrophoresis) to quantitatively analyze the structural and
functional determinants of the core and linker histone terminal domains
and MeCP2. The lab also specializes in characterizing the architectural
features of large chromatin-based assemblages in solution.
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Structural
Dynamics of Nucleosomal Arrays and Chromatin Fibers: the Core and Linker
Histones
MeCP2 in
Health and Disease
Intrinsic
Disorder in Proteins
Historical Perspective:
Key
Papers that Led Us to This Point
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