Dr. Brian
David Strahl a licensed chromatin biologist at the University of North
Carolina. Together with his group, they have been in the forefront of
discovering how small how small chemical additions or molecular “tags” on
histone proteins balance the accessibility of DNA and the genetic information
it contains. Histones are central point to the organization of our DNA in
cells. These proteins come in different
types or isoforms such as H3, H4, H2A and H2B, and they link with themselves as
a means to package our DNA within the small nuclei of cells. Two copies each of
each histone type come together to create what is called an octamer, which
wraps about 147 base pairs of DNA around it.
This structure (histones + DNA) makes up the basic building block of
chromatin which is called the nucleosome. The strings of nucleosomes develop
the chromatin fiber and they systematize into higher-order structures that are
poorly determined but allow large genomes(e.g., ~3.4 billion base pairs making
up the human genome) to fit in the confines of a 2-10 micron nucleus. This extraordinary level of compaction is
further interfered by the actions of a 5th histone type known as
linker histone H1.
With all
his compaction,
the number question is how our genome is made accessible at the right place and
time for all of the essential processes that happens with DNA (such as gene
expression, DNA repair and replicating the genome). As it turns out, histones, and the
nucleosomes they form, are the major administrators of chromatin compaction and
decompaction. Just about every process needs protein machineries that bind
it. Each of these machineries is highly
tuned to collaborate with, and control, the histones that wrap DNA.
Huge
mechanisms by which histones are controlled to alter the accessibility of DNA
are the chemical modifications or molecular “tags” that are placed on them.
Many enzymes have been classified over the last few decades that add (i.e.,
write) or eliminate (i.e., erase) these histone modifications. The chemical
tags serve as signals or messages to inform chromatin how to act whether to
have open or close, and/or express a gene or not. The question of how these chemical
tags work have been at the core of many researches and studies. Some shows that
the histone modifications either act in a physically manner to change
nucleosome solidity or nucleosome-nucleosome interactions, or by recruiting
“effector” proteins that then carry out the biological function. A huge number
of histone modifications have been examined, which happen on each histone type.
Moreover, many effect proteins making use specialized domains have been found
to read these histone marks. While much has been known in the area of histone
function, a great deal more work is needed to figure out how histone
modifications impact chromatin structure and function. This very critical as recent and past studies
is discovering that many human mutations that are linked with diseases such as
cancer happen in the histones themselves or the protein machineries that are ramified
in histone/DNA regulation. In his lad,
he determine how the protein machineries that handle histones are employed to
chromatin, how histone modifications become protected and safe, and then how
these modifications are read or interpreted to advance
chromatin function.
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