Conservation of dichromatin organization along regional centromeres
The attachment of the kinetochore to the centromere is essential for genome maintenance, yet the highly repetitive nature of satellite regional centromeres limits our understanding of their chromatin organization. We demonstrate that single-molecule chromatin fiber sequencing (Fiber-seq) can uniquely co-resolve kinetochore and surrounding chromatin architectures along point centromeres, revealing largely homogeneous single-molecule kinetochore occupancy. In contrast, the application of Fiber-seq to regional centromeres exposed marked per-molecule heterogeneity in their chromatin organization. Regional centromere cores uniquely contain a dichotomous chromatin organization (dichromatin) composed of compacted nucleosome arrays punctuated with highly accessible chromatin patches. CENP-B occupancy phases dichromatin to the underlying alpha-satellite repeat within centromere cores but is not necessary for dichromatin formation. Centromere core dichromatin is conserved between humans and primates, including along regional centromeres lacking satellite repeats. Overall, the chromatin organization of regional centromeres is defined by marked per-molecule heterogeneity, buffering kinetochore attachment against sequence and structural variability within regional centromeres.
Authors
- Adriana E. Sedeño-Cortés (ORCID: https://orcid.org/0000-0001-7959-8970)
- Sue Biggins (ORCID: https://orcid.org/0000-0002-4499-6319)
- Taylor Real (ORCID: https://orcid.org/0000-0001-9691-8710)
- Glennis A. Logsdon (ORCID: https://orcid.org/0000-0003-2396-0656)
- Evan E. Eichler (ORCID: https://orcid.org/0000-0002-8246-4014)
- Rachel J. O’Neill (ORCID: https://orcid.org/0000-0002-1525-6821)
- Benjamin J. Mallory (ORCID: https://orcid.org/0000-0003-1572-6181)
- Gabrielle A. Hartley (ORCID: https://orcid.org/0000-0002-5672-2171)
- Danilo Dubocanin (ORCID: https://orcid.org/0000-0003-0330-5814)
- Aman Agarwal (ORCID: https://orcid.org/0009-0005-5813-7047)
- Andrew B. Stergachis (ORCID: https://orcid.org/0000-0002-1299-3674)
- Yizi Mao (ORCID: https://orcid.org/0000-0001-5743-6831)
- Katherine M. Munson (ORCID: https://orcid.org/0000-0001-8413-6498)
- Sabrine Hédouin (ORCID: https://orcid.org/0000-0002-3977-1852)
- Jane Ranchalis
Institutions
- Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa (ZA)
- Howard Hughes Medical Institute (US)
- Howard University (US)
- University of Connecticut (US)
- University of Washington (US)
- University of Washington Medical Center (US)
- Fred Hutch Cancer Center (US)
- Brotman Baty Institute (US)
Publication Details
- Journal
- Cell Genomics
- Published
- 2025-03-27
- DOI
- https://doi.org/10.1016/j.xgen.2025.100819
- Citations
- 12
- Primary Topic
- Genomics and Chromatin Dynamics
- Type
- article
- Field-Weighted Citation Impact
- 8.87
Funders
- Howard Hughes Medical Institute
- Burroughs Wellcome Fund
- Pew Charitable Trusts
- National Human Genome Research Institute
- National Institute of General Medical Sciences