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has long been assumed that there must be chromosomal proteins other than
linker histones that bind nucleosomes and influence local and global
chromatin architecture. However, only recently have some of these proteins
been identified and studied in biochemically pure systems.
Our studies of chromatin architectural proteins focus on yeast silencing
proteins (SIR2, SIR3 and SIR4), and human MeCP2. The SIR proteins interact
with themselves and chromatin to form transcriptionally silenced
heterochromatin. We are currently dissecting the mechanisms and determinants
of the protein-protein and protein-chromatin interactions involved in
SIR-dependent formation of heterochromatin in vitro. MeCP2 is a methyl DNA
binding protein that also possesses a remarkably potent ability to condense
chromatin fibers into unique secondary (right) and tertiary chromatin
structures. Mutations in MeCP2 are causative of the neurological disorder,
Rett Syndrome, and we are very interested in characterizing the mechanisms
involved in native and mutant MeCP2 interaction with chromatin, and the
resulting secondary and tertiary chromatin structure chromatin structures
formed by such interactions.
One very important thing that has become evident from in vitro studies of
chromatin architectural proteins is that the term “higher order chromatin
structure” in no longer particularly informative. Many specific types of
higher order chromatin structures have now been identified depending of the
specific nucleoprotein composition of the chromatin fiber. Consequently, we
now think about chromatin fiber architecture in the way protein chemists
thinks about folding of polypeptide chains. Chromatin fibers fold into
distinct secondary and tertiary chromatin structures whose structural
features are linked to genome function. Proteins do not function as unfolded
polypeptide chains, and neither do chromatin fibers.
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