REVIEW article
Front. Cell Dev. Biol.
Sec. Chromosome and Chromatin Biology
Keeping it centered: Decoding the activities that regulate yeast histone H3 variant Cse4 and confine it to centromeres
Provisionally accepted
- University of Trento, Trento, Italy
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
The field of centromere biology was launched in 1980 with the isolation of a 120-bp centromeric DNA fragment from Saccharomyces cerevisiae. Fifteen years later, the discovery that the yeast histone H3 variant Cse4 is the conserved counterpart of human CENP-A established both proteins as the defining epigenetic marks of centromeres. Subsequent genetic screens, molecular biological and biochemical studies have elucidated how Cse4 is specifically targeted to and stably maintained at centromeres. The mislocalization of Cse4 beyond centromeres disrupts transcriptional programs, and drives chromosomal instability and aneuploidy. This review traces Cse4 research from its early breakthroughs to current insights into its regulatory pathways. Although derived from yeast, these mechanistic advances provide a conceptual framework for understanding analogous, and likely conserved, processes in humans, where CENP-A biology remains less well defined but is increasingly being implicated in cancer and therapy resistance when perturbed.
Keywords: CENP-A, Centromere, Cse4, kinetochore, Psh1, Scm3
Received: 06 Jan 2026; Accepted: 10 Feb 2026.
Copyright: © 2026 Greco, Klim and De Wulf. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Peter De Wulf
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.