Evidence map›Paper›PMID 42560819›Full record

ArticleCell reports2026

Neocentromeres fail to maintain DNA methylation boundaries, driving CENP-A drift, instability, and chromosome missegregation.

Megan A Mahlke, Angela Enriquez, Lior Lumerman, Poulomi Nath, Cy Chittenden, Savannah Hoyt, Jonas Koeppel, Yuan Xu, Rebecca Raphael, Kylie Zaffina and 7 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors.

Megan A MahlkeUPMC Hillman Cancer Center, Pittsburgh, PA 15213, USA; Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA 15261, USA.
Angela EnriquezUPMC Hillman Cancer Center, Pittsburgh, PA 15213, USA; Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA 15261, USA.
Lior LumermanUPMC Hillman Cancer Center, Pittsburgh, PA 15213, USA; Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA 15261, USA.
Poulomi NathUPMC Hillman Cancer Center, Pittsburgh, PA 15213, USA; Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA 15261, USA.
Cy ChittendenDepartment of Genetics, School of Medicine, Stanford University, Stanford, CA, USA.
Savannah HoytDepartment of Molecular and Cell Biology, University of Connecticut, Storrs, CT, USA; Department of Genetics and Genome Sciences, UConn Health, Farmington CT, USA.
Jonas KoeppelSomatic Genomics Programme, Wellcome Sanger Institute, Hinxton, UK.
Yuan XuUC Santa Cruz Genomics Institute, Santa Cruz, CA, USA.
Rebecca RaphaelUPMC Hillman Cancer Center, Pittsburgh, PA 15213, USA; Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA 15261, USA.
Kylie ZaffinaUPMC Hillman Cancer Center, Pittsburgh, PA 15213, USA; Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA 15261, USA.
Paul W HookDepartment of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA.
Winston TimpDepartment of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA.
Karen H MigaUC Santa Cruz Genomics Institute, Santa Cruz, CA, USA.
Peter J CampbellSomatic Genomics Programme, Wellcome Sanger Institute, Hinxton, UK.
Rachel J O'NeillDepartment of Molecular and Cell Biology, University of Connecticut, Storrs, CT, USA; Department of Genetics and Genome Sciences, UConn Health, Farmington CT, USA.
Nicolas AltemoseDepartment of Genetics, School of Medicine, Stanford University, Stanford, CA, USA.
Yael Nechemia-ArbelyUPMC Hillman Cancer Center, Pittsburgh, PA 15213, USA; Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA 15261, USA. Electronic address: arbelyy@upmc.edu.

Funding

VECTOR CORE FACILITYP30CA047904 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI CHRISTOPHER J. BAKKENIST · 1988 to 2026
$158.0M
Nanopore based profiling of epigenetic stateR01HG009190 · NHGRI · JOHNS HOPKINS UNIVERSITY · PI TIMP, WINSTON GEORGE · 2017 to 2024
$4.8M
Supplement to Promote Diversity: Mechanisms of epigenetic assembly, maintenance and propagation of human centromeresR35GM142717 · NIGMS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI NECHEMIA-ARBELY, YAEL · 2021 to 2025
$2.3M
The Role of Retroelements in Centromere FunctionR01GM123312 · NIGMS · UNIVERSITY OF CONNECTICUT STORRS · PI O'NEILL, RACHEL · 2019 to 2022
$1.9M
High-Throughput Computing for Genomics and Bioinformatics ResearchS10OD028483 · OD · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI LEE, ADRIAN V · 2021 to 2021
$574k
NCI NIH HHS P30 CA047904NHGRI NIH HHS R01 HG009190NIGMS NIH HHS R01 GM123312NIGMS NIH HHS R35 GM142717NIH HHS S10 OD028483
6 · The paper itself

Abstract

Centromere identity is specified by CENP-A, a histone H3 variant that epigenetically defines centromere position. How CENP-A is maintained at one location in rapidly evolving centromeric DNA is unknown. Using single-cell-derived clones of human cell lines, we demonstrate heterogeneity in CENP-A position within cell populations at neocentromeres and a native centromere. CENP-A heterogeneity is accompanied by heterogeneous DNA methylation patterns, with DNA methylation shifting according to CENP-A position. We demonstrate centromere epigenetic plasticity over extended proliferation, with native centromeres maintaining stable DNA methylation boundaries, but neocentromeres exhibiting DNA methylation instability, boundary loss, and increased missegregation. Finally, we show that neocentromeres are more sensitive to DNA methylation inhibition than native centromeres, and that this inhibition is accompanied by expanded CENP-A-enriched domains and increased missegregation. This study supports a role for DNA methylation boundaries in maintaining centromere position, stability, and function and highlights the intrinsic instability of DNA methylation at neocentromeres.

Indexed as

CENP-Acentromere maintenancecentromereschromatinCP: cell biologyCP: molecular biologyDNA methylationepigeneticsgenomic stabilityheterochromatinneocentromeres

Identifiers

PMID42560819
PMCPMC13595371

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.