The epigenetic regulation of centromeres and telomeres in plants and animals

Abstract

The centromere is a chromosomal region where the kinetochore is formed, which is the attachment point of spindle fibers. Thus, it is responsible for the correct chromosome segregation during cell division. Telomeres protect chromosome ends against enzymatic degradation and fusions, and localize chromosomes in the cell nucleus. For this reason, centromeres and telomeres are parts of each linear chromosome that are necessary for their proper functioning. More and more research results show that the identity and functions of these chromosomal regions are epigenetically determined. Telomeres and centromeres are both usually described as highly condensed heterochromatin regions. However, the epigenetic nature of centromeres and telomeres is unique, as epigenetic modifications characteristic of both eu- and heterochromatin have been found in these areas. This specificity allows for the proper functioning of both regions, thereby affecting chromosome homeostasis. This review focuses on demonstrating the role of epigenetic mechanisms in the functioning of centromeres and telomeres in plants and animals.

Keywords: cytosine methylation; histone code; non-coding RNA; pericentromeric; subtelomeric.

Figure 1.

Model of the vertebrate mitotic centromere/kinetochore complex. Kinetochores assemble on chromatin marked by CENP-A containing nucleosomes. CENP-A nucleosome binds chromosomal passenger complex (CPC), which consists of four proteins: kinase Aurora B, INCENP, Survivin and Borealin. The kinetochore is composed mainly of CCAN (constitutive centromere-associated network) and Knl1-Mis12-Ndc80 complexes. The presence of CENP-A allows the recruitment of CCAN, which is a complex consisting of 16 centromeric proteins: CENP-C, CENP-T-W-S-X, CENP-H-I-K-M, CENP-N-L and CENP-O-P-Q-R-U. CENP-C and CENP-N bind CENP-A. The CENP-T-W-S-X complex creates a unique nucleosome-like structure that allows DNA binding in centromeric chromatin. CENP-N-L and CENP-H-I-K-M have regulatory roles. CENP-H-I-K-M-L-N help recruit CENP-C. CENP-C binds to the Mis12 complex, which then recruits Knl1 proteins interacting with microtubules and the Ndc80 complex. Ndc80 – kinetochore complex component (the complex consists of Ndc80-Nuf2-Spc24-Spc25 proteins); cenH3 – centromere specific histone 3 or histone H3 variant found at the centromere, CENP-A – centromere protein A, centromere specific histone 3 or histone H3 variant found at the centromere; CENP-C – centromere protein C; Mis 12 Complex – complex of the core kinetochore (the complex consists of Mis12-Dsn1-Nnf1-Nsl1 proteins); Knl1 – kinetochore scaffold 1; Zwint – kinetochore proteins; CCAN – constitutive centromere-associated network, CPC – chromosomal passenger complex (consisting of Borealin, Survivin, INCENP, and the Aurora B kinase), INCENP – Inner Centromere Protein; Ska Complex – spindle and kinetochore associated (the complex consists of Ska1-Ska2-Ska3 proteins).

Figure 2.

Epigenetic modifications in centromeric and pericentric chromatin. Centromeres consist of alternating blocks of nucleosomes containing H3 or cenH3. At pericentric sites, only H3-containing nucleosomes are present. Epigenetic markers in centomere and pericentromere regions characteristic for both plants and animals are marked with black color, only for plants with violet color, only for animals with rose color. (+) epigenetic marker always present; (-/+) epigenetic modification present or absent.

Figure 3.

Telomere structure in mammals; T-loop and D-loop are presented together with schematic representation of the shelterin complex on telomeric DNA. The shelterin complex consists of six proteins: TRF1 and TRF2 (telomere repeat-binding factor 1 and 2), RAP1 (repressor/activator protein 1), TIN2 (TRF1-interacting nuclear factor 2), TPP1 (TINT1/PTOP/PIP1 protein) and POT1 (protection of telomeres 1).

Figure 4.

Epigenetic modifications in telomere and subtelomere chromatin and adjacent euchromatin. Epigenetic markers in telomere and subtelomere regions characteristic for both plants and animals are marked with black color, only for plants with violet colour, only for animals with rose color.