Biology Reference
In-Depth Information
2000
). The state of the chromatin can control the transcriptional state of a
cell and the accessibility to its DNA. As pointed earlier, the two major chro-
matin states, the euchromatin and the heterochromatin, fluctuate dynami-
cally and it is thought that they are only stabilized once the cells reach
their “final” differentiation status. In this sense, the global state of the chro-
matin could for instance be considered to define the state of potency and
plasticity of a cell, through the control of the accessibility to specific
sequences of the DNA. In order to dynamically alter nucleosome spacing
and/or accessibility, several mechanisms have been described that might
in some instances work in a cooperative basis. These include (i) ATP-
dependent chromatin remodelers, (ii) DNA methylation (and hydro-
xymethylation), (iii) histone modifications, (iv) incorporation of specific
histone variants, and (v) the nuclear architecture, including the position that
a given genomic region occupies within the nucleus.
The constitutive heterochromatin is marked by posttranslational modi-
fications both on the N-terminus of histone tails and in the nucleosomal core
region, in particular, by the enrichment of H3K9me3, H3K64me3, and
H4K20me3 (
Daujat et al., 2009; Peters et al., 2001; Schotta et al., 2004
).
This state of chromatin is localized to centromeric and pericentromeric
regions as well as telomeric regions (the latter only containing H3K9me3)
and is also known to be deacetylated (
Grewal & Elgin, 2007
). Repetitive
elements in mammalian genomes are also known to be silenced through
the acquisition of a constitutive heterochromatic signature (see Sections
3.5 and 3.6). While the constitutive heterochromatin is considered to assem-
ble mainly at gene poor regions and repetitive elements, the facultative het-
erochromatin can be present in gene-rich regions that can switch their state
between euchromatin and heterochromatin depending on multiple factors
(
Bernstein et al., 2006
). The facultative heterochromatin is characterized by
a strong enrichment of H3K27me3 and the related PRC1-catalyzed
ubiquitination of H2AK119 (
Grewal & Elgin, 2007
).
Most posttranslational modifications of histones described to date,
including phosphorylation, acetylation, and ubiquitination, are mono-
layered, which means that they have only one level of modification. In con-
trast, methylation of lysine residues has been described to occur at three
layers: mono-, di-, and trimethylation, each of them with apparent different
downstream effects. Indeed, this gives rise to different chromatin landscapes
and/or recognition motifs at each layer of modification that can be read or
modified by different types of readers and remodelers (
Bonasio, Tu, &
Reinberg, 2010; Kouzarides, 2007; Santos-Rosa et al., 2002
). This has been
