SHOWCASE ON RESEARCH
EDITORIAL
Deviant Nucleosomes: the Functional Specialisation of Chromatin
To my (unbiased) mind, the most amazing
macromolecular structure in nature is chromatin. To
illustrate this point, imagine trying to squeeze over
10,000 km of spaghetti into a soccer ball. This analogy
describes the level of packaging that must occur in order
to fit over 2 metres of our DNA per cell into a nucleus
of about 20 µm in diameter. However, this is only part
of the problem. Imagine then how this 10,000 km of
spaghetti following its duplication when the soccer
ball replicates and divides, separates into two copies of
daughter spaghetti without them becoming entangled.
This analogy describes what must take place every time
our genome divides. This complex engineering problem
has been solved by partitioning and dividing our
genome into stable identities, the chromosomes, which
are capable of being transported to the opposite ends of
a dividing cell.
Chromosomes are comprised of chromatin, a dynamic
complex between DNA and histones. The basic building
block of chromatin is the nucleosome, which represents
the first level of compaction. A nucleosome is comprised
of approximately two negative superhelical turns of
genomic DNA (about 160 base pairs) wrapped around
a protein complex consisting of eight histone molecules
(two molecules each of histone H2A, H2B, H3, and H4,
which form an octamer) as shown on the front cover
of this issue. Individual nucleosomes are subsequently
organised into a regular array, with flexible linker DNA
(around 40 base pairs) between them, which ultimately
folds and compacts to produce a chromosome (how this
folding occurs is still a matter of much debate). However,
while the formation of chromatin solves the packaging
problem, it creates another, which is, how do genes and
their promoters become accessible to the transcription
machinery given this incredible level of compaction.
The answer, in part, resides in the fact that the
David Tremethick
John Curtin School of Medical Research, ANU, Canberra, ACT 2601
Cover Illustration
The structure of a nucleosome core particle.
Image courtesy of Daniel Ryan, John Curtin
School of Medical Research, Australian National
University.
In the next issue... In August, the
Showcase on Research will be on
Computational Biology of Proteins –
Guest Editor: Alan Mark
Australian Biochemist – Editor Chu Kong Liew,
Editorial Officer Liana Friedman
© 2014 Australian Society for Biochemistry and
Molecular Biology Inc. All rights reserved.
Vol 45 No 1 April 2014
nucleosome has evolved to become a multisubunit
structure, rather than one large protein wrapping the
160 base pairs of DNA. This multisubunit structure has
two critical structural and functional implications. First,
the nucleosome can rapidly assemble and disassemble,
thus enabling promoter access. Second, the nucleosome
has an enormous potential to be modified by selective
post-translational modifications of each individual
histone and by the replacement of a canonical histone
with its histone variant form (histone variants are nonallelic deviant forms of the canonical histones that vary
in their primary sequence). Therefore, the chromosome
itself has been divided and partitioned into functionally
specialised domains dependent upon their makeup of
histone variants and specific histone posttranslational
modifications (note that adding to this complexity, a
nucleosome can contain either one or two copies of a
histone variant, which can also have a dramatic effect
on function).
In this Showcase on Chromosomes, Chromatin and
Transcriptional Regulation, we will highlight how this
functional specialisation of chromatin ensures that:
(i) following cell division, each daughter cell receives
only one copy of each chromosome (the centromere),
(ii) the ends of chromosomes are not eroded away (the
telomere) and (iii) the promoter can be assembled into
a structure that is accessible to the RNA polymerase
II transcription machinery (in a ubiquitous or tissuespecific manner). This chromatin-based information
at the genome-wide level has been referred to as the
epigenome (meaning ‘above’ the genome). Finally, we
will learn how understanding the nature and function
of the epigenome is at the ‘heart’ of understanding and
improving the reprogramming of somatic cells into
induced pluripotent stem cells, which offers so much
promise to the field of regenerative medicine.
[email protected]
Chromosomes, Chromatin and
Transcriptional Regulation
Guest Editor: David Tremethick
4 CENP-A: the Centromere-specific Histone Anchorman
Paul Kalitsis
7 Telomere Epigenetics in Stem Cells and Cancers
Lyn Chan and Lee Wong
12 Histone Variant Selectivity at the Transcription Start
Site: H2A.Z or H2A.Lap1
Maxim Nekrasov, Tatiana Soboleva, Cameron Jack and
David Tremethick
17 Epigenetic Changes During Reprogramming
Sara Alaei, Anja Knaupp and Jose Polo
AUSTRALIAN BIOCHEMIST
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