Biology Reference
In-Depth Information
1. INTRODUCTION AND EVOLUTIONARY PERSPECTIVE
The eukaryotic genome is organized in the nucleus of a cell as
chromatin—a dynamic and highly organized DNA-histone complex. In the
nucleus of an interphasecell, chromatin appears as twodistinct subtypes referred
to as euchromatin and heterochromatin. Euchromatin is decondensed, gene
rich, replicates early, and is enriched for histone posttranslational modifications
(PTMs) associated with active transcription (i.e.. H3 lysine 4 di-/tri-methyla-
tion (H3K4me2/3), H3K36me2/3). In contrast, heterochromatin remains
compacted throughout the cell cycle, contains repetitive sequences, replicates
late in S phase, and is enriched for DNAmethylation and histone PTMs related
to transcriptional silencing (i.e., H3K9me3,H4K20me3) (
Probst, Dunleavy, &
Almouzni, 2009
). These different chromatin marks have been intensively
mapped to the genome of various model organisms and correlated to key bio-
logical processes (
Campos & Reinberg, 2009; Consortium T.E.P., 2012;
Gerstein et al., 2010; Kouzarides, 2007; Roy et al., 2010
). Multicellular organ-
isms originate froma single totipotent cell, the zygote that gives rise to a variety
of cell types, which share the same genome but differ greatly in their morphol-
ogy, function, and chromatin structure. This developmental diversity is
achieved by complex genome regulation, involving transcription factors and
chromatin modifiers.
In this review, we will specifically focus on two major chromatin repres-
sive pathways. The first one is the H3K9/HP1 pathway, which involves
lysine-specific methyltransferases (KMTs) that methylate H3K9, a mark rec-
ognized by the chromodomain (CD) containing family of HP1 proteins.
The second one is the Polycomb repressive pathway, which in mammals
is classically related to gene silencing by two distinct complexes, Polycomb
repressive complexes 1 and 2 (PRC1 and PRC2) and the associated PTMs
H2AK119ub1 and H3K27me3, respectively.
Both pathways are conserved throughout eukaryotic evolution, since
homologues for the core components are found in animals, plants, and fungi
(
Garcia et al., 2007; Krauss, 2008; Schuettengruber, Chourrout, Vervoort,
Leblanc, & Cavalli, 2007; Shaver, Casas-Mollano, Cerny, & Cerutti, 2010
).
In fact, both H3K9 and H3K27 methylation have been found in unicellular
algae and protozoa, which suggest that this type of chromatin regulation has
a very early origin (
Krauss, 2008; Liu et al., 2007; Shaver et al., 2010
).
Furthermore, it seems that the two pathways not only have a common
origin but possibly shared the same biological function. In the protozoa
Tet-
rahymena thermophila
, Ezl1 (the homologue of the PRC2 KMT Ezh2)
