Evidence map›Paper›PMID 41720070›Full record

ArticleNeoplasia (New York, N.Y.)2026

Genetic loss of CHD1 regulates distinct histone post-translational modifications in the development of castration-resistant prostate cancer.

Tanaya A Purohit, Joseph Gawdzik, Eric A Armstrong, Bing Yang, Zachery Schultz, Kayla Bahr, Truman J Do, Rehaan Machhi, Sean Sardeson, Mohammad Rizvi and 9 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neoplasia (New York, N.Y.), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

19 authors.

Tanaya A PurohitDepartment of Urology, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53705, USA; Cancer Biology Program, University of Wisconsin, Madison, WI 53706, USA.
Joseph GawdzikDepartment of Urology, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53705, USA.
Eric A ArmstrongWisconsin Institute for Discovery and the Morgridge Institute for Research, University of Wisconsin, Madison, WI 53715, USA.
Bing YangDepartment of Urology, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53705, USA.
Zachery SchultzDepartment of Urology, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53705, USA; Cancer Biology Program, University of Wisconsin, Madison, WI 53706, USA.
Kayla BahrDepartment of Urology, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53705, USA.
Truman J DoDepartment of Biomolecular Chemistry, University of Wisconsin, Madison, WI 53706, USA.
Rehaan MachhiDepartment of Urology, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53705, USA.
Sean SardesonDepartment of Urology, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53705, USA.
Mohammad RizviDepartment of Urology, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53705, USA.
Sarah A NakadaDepartment of Urology, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53705, USA.
Anupama SinghDepartment of Pathology and Laboratory Medicine, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53705, USA.
Karla EsbonaDepartment of Pathology and Laboratory Medicine, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53705, USA.
Wei HuangDepartment of Pathology and Laboratory Medicine, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53705, USA.
Marjorie L RoskesDepartment of Systems and Computational Biomedicine, Weill Cornell Medicine, New York, NY 10021, USA.
Ekta KhuranaDepartment of Systems and Computational Biomedicine, Weill Cornell Medicine, New York, NY 10021, USA.
Peter W LewisCarbone Comprehensive Cancer Center, University of Wisconsin, Madison, WI 53705, USA; Department of Biomolecular Chemistry, University of Wisconsin, Madison, WI 53706, USA; Cancer Biology Program, University of Wisconsin, Madison, WI 53706, USA.
John M DenuCarbone Comprehensive Cancer Center, University of Wisconsin, Madison, WI 53705, USA; Department of Biomolecular Chemistry, University of Wisconsin, Madison, WI 53706, USA; Wisconsin Institute for Discovery and the Morgridge Institute for Research, University of Wisconsin, Madison, WI 53715, USA.
David F JarrardDepartment of Urology, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53705, USA; Carbone Comprehensive Cancer Center, University of Wisconsin, Madison, WI 53705, USA; Cancer Biology Program, University of Wisconsin, Madison, WI 53706, USA. Electronic address: jarrard@urology.wisc.edu.

Funding

Integrated Training For Physician-ScientistsT32GM140935 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI Anna Huttenlocher, Jeniel E Nett · 2021 to 2026
$6.5M
Dynamics and molecular mechanisms linking metabolism and the epigenomeR35GM149279 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI JOHN M DENU · 2023 to 2026
$2.8M
NIGMS NIH HHS R35 GM149279NIGMS NIH HHS T32 GM140935
6 · The paper itself

Abstract

Epigenetic alterations accumulate with the development of castration resistance in prostate cancer (PC), yet an understanding of how these patterns arise remains incompletely defined. Through histone post-translational modification (PTMs) profiling in paired hormone-sensitive (HS) and castration-resistant (CR) patient-derived xenografts, we identified a novel chromatin state characterized by CHD1 deficiency and global reductions in H3.3K27 and H3.3K36 methylation, which occurred with castration resistance development. Compared to wildtype, CHD1-deficient tumors exhibited lower expression and enzymatic activity of the histone-modifying enzymes (HMEs) NSD2 and EZH2-key regulators of the altered histone PTM landscape. Gene expression analysis of human CRPC samples revealed strong positive correlations among CHD1, NSD2, and EZH2. CHD1 knockout (KO) in CRPC cell lines confirms reduced H3.3K27K36 methylation and downregulation of NSD2 and EZH2. Results from mechanistic studies support a process in which CHD1 occupancy at the promoter regions of NSD2 and EZH2 facilitates transcription via enhanced chromatin accessibility and increased deposition of the activating histone mark H3K4me3. In contrast, CHD1-KO led to promoter accumulation of repressive H3K27me3 modifications. CHD1-KO downregulates interferon (IFN) signaling, including viral mimicry and IFN-stimulated genes. Bulk RNA-sequencing and ChIP-qPCR analyses confirmed co-regulation of these genes by CHD1 and NSD2, coinciding with reduced H3K36me2 enrichment. Notably, this CHD1-deficient epigenetic state confers resistance to NSD2 inhibition. These findings highlight a previously unrecognized role in tumor resistance for CHD1 in modulating HMEs that may influence lineage plasticity as well as suggest new avenues for personalized therapeutic strategies targeting CHD1-specific epigenetic vulnerabilities.

Indexed as

DNA-Binding ProteinsDNA HelicasesHistonesProstatic Neoplasms, Castration-ResistantProtein Processing, Post-TranslationalAnimalsCell Line, TumorEnhancer of Zeste Homolog 2 ProteinEpigenesis, GeneticGene Expression Regulation, NeoplasticHistone-Lysine N-MethyltransferaseHumansMaleMethylationMiceRepressor ProteinsCHD1 protein, humanDNA-Binding ProteinsDNA HelicasesEnhancer of Zeste Homolog 2 ProteinHistone-Lysine N-MethyltransferaseHistonesNSD2 protein, humanRepressor ProteinsCastration resistant prostate cancer (CRPC)CHD1EpigeneticsEZH2Histone methylationNSD2

Identifiers

PMID41720070
PMCPMC12933292

What OpenQuestion holds

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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.