Evidence map›Paper›PMID 33741908›Full record

ArticleNature communications2021

CRISPRi screens reveal a DNA methylation-mediated 3D genome dependent causal mechanism in prostate cancer.

Musaddeque Ahmed, Fraser Soares, Ji-Han Xia, Yue Yang, Jing Li, Haiyang Guo, Peiran Su, Yijun Tian, Hyung Joo Lee, Miranda Wang and 22 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed
13.5field-weighted citation impact, top 1% of its field
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

41 citing papers in PubMed, 62 citations in OpenAlex.

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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

32 authors at 12 institutions in 4 countries.

Musaddeque Ahmed *Princess Margaret Cancer Center/University Health Network, Toronto, ON, Canada.
Fraser Soares *Princess Margaret Cancer Center/University Health Network, Toronto, ON, Canada.ORCID 0000-0002-3977-7939
Ji-Han Xia *Faculty of Biochemistry and Molecular Medicine, Biocenter Oulu, University of Oulu, Oulu, Finland.
Yue YangChanghai Hospital, Shanghai, China.
Jing LiChanghai Hospital, Shanghai, China.
Haiyang GuoPrincess Margaret Cancer Center/University Health Network, Toronto, ON, Canada.
Peiran SuPrincess Margaret Cancer Center/University Health Network, Toronto, ON, Canada.
Yijun TianDepartment of Tumor Biology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
Hyung Joo LeeDepartment of Genetics, Washington University in St. Louis, St. Louis, MO, USA.ORCID 0000-0002-7030-5390
Miranda WangPrincess Margaret Cancer Center/University Health Network, Toronto, ON, Canada.
Nayeema AkhtarPrincess Margaret Cancer Center/University Health Network, Toronto, ON, Canada.
Kathleen E HoulahanDepartment of Medical Biophysics, University of Toronto, Toronto, ON, Canada.ORCID 0000-0002-2273-2099
Almudena BoschDepartment of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Stanley ZhouPrincess Margaret Cancer Center/University Health Network, Toronto, ON, Canada.ORCID 0000-0001-8187-0128
Parisa MazrooeiPrincess Margaret Cancer Center/University Health Network, Toronto, ON, Canada.
Junjie T HuaPrincess Margaret Cancer Center/University Health Network, Toronto, ON, Canada.
Sujun ChenPrincess Margaret Cancer Center/University Health Network, Toronto, ON, Canada.
Jessica PetriccaPrincess Margaret Cancer Center/University Health Network, Toronto, ON, Canada.
Yong ZengPrincess Margaret Cancer Center/University Health Network, Toronto, ON, Canada.
Alastair DaviesThe Vancouver Prostate Centre, Vancouver General Hospital and Department of Urologic Sciences, The University of British Columbia, Vancouver, BC, Canada.
Michael FraserPrincess Margaret Cancer Center/University Health Network, Toronto, ON, Canada.
David A QuigleyHelen Diller Family Comprehensive Cancer Center, University of California at San Francisco, San Francisco, CA, USA.
Felix Y FengHelen Diller Family Comprehensive Cancer Center, University of California at San Francisco, San Francisco, CA, USA.ORCID 0000-0002-0963-7687
Paul C BoutrosVector Institute, Toronto, ON, Canada.ORCID 0000-0003-0553-7520
Mathieu LupienPrincess Margaret Cancer Center/University Health Network, Toronto, ON, Canada.
Amina ZoubeidiThe Vancouver Prostate Centre, Vancouver General Hospital and Department of Urologic Sciences, The University of British Columbia, Vancouver, BC, Canada.ORCID 0000-0002-0498-142X
Liang WangDepartment of Tumor Biology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.ORCID 0000-0002-9364-8572
Martin J WalshDepartment of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Ting WangDepartment of Genetics, Washington University in St. Louis, St. Louis, MO, USA.
Shancheng RenChanghai Hospital, Shanghai, China. renshancheng@gmail.com.ORCID 0000-0001-9205-7888
Gong-Hong WeiFaculty of Biochemistry and Molecular Medicine, Biocenter Oulu, University of Oulu, Oulu, Finland. gonghong_wei@fudan.edu.cn.ORCID 0000-0001-6546-9334
Housheng Hansen HePrincess Margaret Cancer Center/University Health Network, Toronto, ON, Canada. hansenhe@uhnresearch.ca.ORCID 0000-0003-2898-3363
University Health Network · CAOntario Institute for Cancer Research · CASecond Military Medical University · CNIcahn School of Medicine at Mount Sinai · USMoffitt Cancer Center · USUniversity of British Columbia · CAUniversity of California, San Francisco · USWashington University in St. Louis · USShanghai Medical College of Fudan University · CNUniversity of California, Los Angeles · USUniversity of Oulu · FIUniversity of Toronto · CA

Funding

Women's CancersP30CA016042 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Samuel Wheeler French · 1985 to 2026
$134.5M
UCLA SPORE in Brain CancerP50CA211015 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Yvonne Yu-Hsuan Chen · 2017 to 2026
$25.2M
Underlying chromatin architecture defines functionality for CFTR expressionR01DK118946 · NIDDK · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI WALSH, MARTIN JOHN · 2018 to 2022
$2.1M
New Epigenetic Gene Silencing TechnologyR01GM119189 · NIGMS · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI WALSH, MARTIN JOHN, ZHOU, MING-MING · 2016 to 2019
$1.8M
Functional characterization of prostate cancer risk loci by high throughput sequencingR01CA250018 · NCI · H. LEE MOFFITT CANCER CTR & RES INST · PI WANG, LIANG · 2020 to 2023
$1.5M
CIHR 142246CIHR 152863CIHR 152864CIHR 153234CIHR 159567NCI NIH HHS P30 CA016042NCI NIH HHS P50 CA211015NCI NIH HHS R01 CA250018NIDDK NIH HHS R01 DK118946NIGMS NIH HHS R01 GM119189
6 · The paper itself

Abstract

Prostate cancer (PCa) risk-associated SNPs are enriched in noncoding cis-regulatory elements (rCREs), yet their modi operandi and clinical impact remain elusive. Here, we perform CRISPRi screens of 260 rCREs in PCa cell lines. We find that rCREs harboring high risk SNPs are more essential for cell proliferation and H3K27ac occupancy is a strong indicator of essentiality. We also show that cell-line-specific essential rCREs are enriched in the 8q24.21 region, with the rs11986220-containing rCRE regulating MYC and PVT1 expression, cell proliferation and tumorigenesis in a cell-line-specific manner, depending on DNA methylation-orchestrated occupancy of a CTCF binding site in between this rCRE and the MYC promoter. We demonstrate that CTCF deposition at this site as measured by DNA methylation level is highly variable in prostate specimens, and observe the MYC eQTL in the 8q24.21 locus in individuals with low CTCF binding. Together our findings highlight a causal mechanism synergistically driven by a risk SNP and DNA methylation-mediated 3D genome architecture, advocating for the integration of genetics and epigenetics in assessing risks conferred by genetic predispositions.

Indexed as

CRISPR-Cas SystemsDNA MethylationAnimalsCarcinogenesisCCCTC-Binding FactorCell Line, TumorGene EditingGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansMaleMiceMice, Inbred NODMice, SCIDPolymorphism, Single NucleotidePromoter Regions, GeneticCCCTC-Binding FactorProto-Oncogene Proteins c-myc

Identifiers

PMID33741908
PMCPMC7979745
OpenAlexW3135981208

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.