Biology Reference
In-Depth Information
3. MECHANISMS OF HETEROCHROMATIN
ESTABLISHMENT AND INHERITANCE
3.1. Heterochromatin establishment and centromeric
chromatin
The histone modification marks that are characteristic of constitutive het-
erochromatin along with the enzymes that produce these modifications
and the proteins that recognize them are highly conserved from fission yeast
to human (
Kouzarides, 2007
). From fission yeast to mammals, methylation
of H3K9 is considered to be crucial for heterochromatin assembly (
Bannister
et al., 2001; Lachner et al., 2001; Rea et al., 2000
). As pointed out earlier, in
mammals several proteins can methylate H3K9, whereas in fission yeast,
Clr4, a single histone H3K9 methyltransferase, directs all methylation of
K9 on histone H3 (
Yamada, Fischle, Sugiyama, Allis, & Grewal, 2005
). Fis-
sion yeast lacks the enzymatic machinery for methylation of H3K27 and is
also devoid of DNA methylation.
The centromere is a well-known landmark of silent chromatin and a
paradigm for epigenetic inheritance. Ultrastructurally, it takes the form of
a distinct primary constriction on the condensed metaphase chromosome
of higher eukaryotes. The constricted region comprises a different chroma-
tin structure consisting of DNA and protein complexes (the kinetochores) to
which microtubules bind to effect proper chromosome movements (
Folco,
Pidoux, Urano, & Allshire, 2008; Pidoux & Allshire, 2005
). The DNA
sequence in the centromere is not conserved between organisms, yet the
centromere displays similar features across evolution such as the presence
of repetitive elements that include the alpha satellite in humans, the minor
satellite inmice, the AATAT and TTCTC satellites in
Drosophila
(
Cleveland,
Mao, & Sullivan, 2003
). Consequently, the sequence requirements, if any,
for a functional centromere are not established.
In fission yeast, the constitutive heterochromatin regions are linked to
centromeres, telomeres, and the mating-type locus. Although there are
some variations, the global mechanisms of heterochromatin assembly on
all these regions are similar. The centromeres in yeast range from 35 to
110 kb in length, with a central domain on which the kinetochore assembles
flanked by outer repeat (
otr
) sequences (consisting of
dg
and
dh
repeats)
coated in heterochromatin that resemble the pericentomeric heterochroma-
tin in mammals (
Steiner, Hahnenberger, & Clarke, 1993; Wood et al.,
2002
). Experiments performed with minichromosomes have demonstrated
