Chromatin remodeling at the centromere
The centromere is the chromosomal locus at which the “kinetochore” is assembled to direct chromosome segregation.
The histone H3 variant, CENP-A, epigenetically marks active centromeres; however a major challenge in centromere biology remains: how do active centromeres guide replacement of histone H3 with CENP-A?
Researchers at KAIST have recently undertaken a research path to help address this question: they demonstrated that centromeres recruit the Ino80 ATP-dependent chromatin remodeling complex independently of underlying DNA sequences to provide an activity required for exchange of histone H3 with CENP-A. In this way, epigenetic propagation is reinforced.
In most eukaryotes, centromeres are specified epigenetically, rather than by underlying DNA sequences. (Epigenetics: Study of gene function changes that involve rentention of same DNA primary sequence and which are heritable and stable).
Histone H3 variant CENP-A, which replaces histone H3 at centromeres, is considered to provide an epigenetic mark for active centromeres.
A model of self-propagating epigenetic centromeres suggests that pre-established CENP-A chromatin at the centromeres is sufficient to direct replenishment of new CENP-A during the cell cycle.
At human centromeres, CENP-A replenishment occurs during the so-called “G1 phase” and is preceded by the replication-independent loss of histone H3.3 incorporated during the “S phase.”
This suggests that centromeres possess a mechanism that actively removes histone H3.3 to make room for CENP-A deposition.
In this paper, we utilized Schizosaccharomyces pombe, a fission yeast.
This organism was chosen because it has epigenetically defined “regional centromeres” whose chromatin and protein compositions are similar to those of their human counterparts, to identify factors responsible for the replacement of histone H3 with CENP-A at centromeres.
In this report, the KAIST research group systematically analyzed the roles of the ATP-dependent chromatin-remodelers in the centromeric chromatin assembly of fission yeast as they serve as strong candidates for such factors.
We find that the Ino80 complex provides the major chromatin remodeling activity required for the replacement of histone H3 with CENP-ACnp1 at regional centromeres of fission yeast.
The researchers therefore propose that the exchange of histone H3-containing nucleosomes with CENP-A nucleosomes by centromere-targeted chromatin-remodeling factors is a conserved theme underpinning the epigenetic propagation of CENP-A chromatin at regional centromeres.
For more information, please refer to the original scientific research article:
Eun Shik Choi, YoungSeo Cheon, Keunsoo Kang and Daeyoup Lee (2017) The Ino80 complex mediates epigenetic centromere propagation via active removal of histone H3. Nat. Commun. 8:529 [doi: 10.1038/s41467-017-00704-3]