Gene Regulation
The lectures will be structured according to the following
schedule: Overview of chromosome structure and gene regulation; The genomic code
for nucleosome positioning; Nucleosome and chromatin dynamics. The genomic DNA
in cells of all higher organisms ("eukaryotes") does not exist as a naked DNA
molecule. Rather, it exists and functions as a highly compacted protein-DNA
complex known as "chromatin", in which the DNA is folded through a
hierarchical series of stages by specialized proteins. In Lecture 1 we will
review what is presently known, and not known, about the three dimensional
structure of chromatin. This discussion will include a review of the structure
of the nucleosome, which is the fundamental structural subunit of chromatin, and
also the subsequent higher levels of organization, about which much less is
known. We will also review of basic mechanisms in eukaryotic gene expression,
activation, and repression. In lecture 2 we will discuss how eukaryotic genomes
dictate their own three dimensional organization, by encoding signals in their
DNA that bias which local regions of the DNA will preferentially be organized
into nucleosomes, and which will preferentially remain nucleosome-free. We will
discuss the underlying physical principles, which are based on the
sequence-dependence of DNA flexibility, and also the biological consequences of
this nucleosome positioning code. In Lecture 3, we will consider how it is that
DNA that is wrapped in nucleosomes, and how nucleosomes that are further wrapped
up in chromatin, nevertheless manage to be biologically active. We will discuss
dynamic properties intrinsic to nucleosomes, and additional dynamics intrinsic
to chains of many nucleosomes, that provide access to the genomic DNA even when
it is organized into such highly folded chromatin fibers.