Publication:
EPIKOL, a chromatin-focused CRISPR/Cas9-based screening platform, to identify cancer-specific epigenetic vulnerabilities

dc.contributor.coauthorPhilpott, Martin
dc.contributor.coauthorCribbs, Adam P.
dc.contributor.coauthorKung, Sonia H.Y
dc.contributor.departmentKUTTAM (Koç University Research Center for Translational Medicine)
dc.contributor.departmentGraduate School of Health Sciences
dc.contributor.departmentSchool of Medicine
dc.contributor.kuauthorAksu, Ali Cenk
dc.contributor.kuauthorBayram, Özlem Yedier
dc.contributor.kuauthorCavga, Ayşe Derya
dc.contributor.kuauthorCingöz, Ahmet
dc.contributor.kuauthorEsin, Beril
dc.contributor.kuauthorKala, Ezgi Yağmur
dc.contributor.kuauthorKayabölen, Alişan
dc.contributor.kuauthorLack, Nathan Alan
dc.contributor.kuauthorMorova, Tunç
dc.contributor.kuauthorÖnder, Tamer Tevfik
dc.contributor.kuauthorÖnder, Tuğba Bağcı
dc.contributor.kuauthorSyed, Hamzah
dc.contributor.kuauthorUyulur, Fırat
dc.contributor.kuauthorGökbayrak, Bengül
dc.contributor.kuauthorKarabıyık, Göktuğ
dc.contributor.kuauthorGünsay, Rauf
dc.contributor.schoolcollegeinstituteGRADUATE SCHOOL OF HEALTH SCIENCES
dc.contributor.schoolcollegeinstituteResearch Center
dc.contributor.schoolcollegeinstituteSCHOOL OF MEDICINE
dc.date.accessioned2024-11-09T13:49:26Z
dc.date.issued2022
dc.description.abstractDysregulation of the epigenome due to alterations in chromatin modifier proteins commonly contribute to malignant transformation. To interrogate the roles of epigenetic modifiers in cancer cells, we generated an epigenome-wide CRISPR-Cas9 knockout library (EPIKOL) that targets a wide-range of epigenetic modifiers and their cofactors. We conducted eight screens in two different cancer types and showed that EPIKOL performs with high efficiency in terms of sgRNA distribution and depletion of essential genes. We discovered novel epigenetic modifiers that regulate triple-negative breast cancer (TNBC) and prostate cancer cell fitness. We confirmed the growth-regulatory functions of individual candidates, including SS18L2 and members of the NSL complex (KANSL2, KANSL3, KAT8) in TNBC cells. Overall, we show that EPIKOL, a focused sgRNA library targeting similar to 800 genes, can reveal epigenetic modifiers that are essential for cancer cell fitness under in vitro and in vivo conditions and enable the identification of novel anti-cancer targets. Due to its comprehensive epigenome-wide targets and relatively high number of sgRNAs per gene, EPIKOL will facilitate studies examining functional roles of epigenetic modifiers in a wide range of contexts, such as screens in primary cells, patient-derived xenografts as well as in vivo models.
dc.description.fulltextYES
dc.description.indexedbyWOS
dc.description.indexedbyScopus
dc.description.indexedbyPubMed
dc.description.issue8
dc.description.openaccessYES
dc.description.publisherscopeInternational
dc.description.sponsoredbyTubitakEuTÜBİTAK
dc.description.sponsorshipScientific and Technological Research Council of Turkey (TÜBİTAK)
dc.description.sponsorshippLenti-CMVBlast-PIP-FUCCI
dc.description.versionPublisher version
dc.description.volume13
dc.identifier.doi10.1038/s41419-022-05146-4
dc.identifier.embargoNO
dc.identifier.filenameinventorynoIR03779
dc.identifier.issn2041-4889
dc.identifier.quartileQ1
dc.identifier.scopus2-s2.0-85135995281
dc.identifier.urihttps://doi.org/10.1038/s41419-022-05146-4
dc.identifier.wos841287000004
dc.keywordsCell line
dc.keywordsTumor
dc.keywordsChromatin
dc.keywordsCRISPR-Cas systems
dc.keywordsEarly detection of cancer
dc.keywordsHumans
dc.keywordsMale
dc.keywordsTriple negative breast neoplasms
dc.language.isoeng
dc.publisherNature Portfolio
dc.relation.grantno1003-216S461
dc.relation.grantno138715
dc.relation.ispartofCell Death and Disease
dc.relation.urihttp://cdm21054.contentdm.oclc.org/cdm/ref/collection/IR/id/10637
dc.subjectCell biology
dc.titleEPIKOL, a chromatin-focused CRISPR/Cas9-based screening platform, to identify cancer-specific epigenetic vulnerabilities
dc.typeJournal Article
dspace.entity.typePublication
local.contributor.kuauthorBayram, Özlem Yedier
local.contributor.kuauthorGökbayrak, Bengül
local.contributor.kuauthorKayabölen, Alişan
local.contributor.kuauthorAksu, Ali Cenk
local.contributor.kuauthorCavga, Ayşe Derya
local.contributor.kuauthorCingöz, Ahmet
local.contributor.kuauthorKala, Ezgi Yağmur
local.contributor.kuauthorKarabıyık, Göktuğ
local.contributor.kuauthorGünsay, Rauf
local.contributor.kuauthorEsin, Beril
local.contributor.kuauthorMorova, Tunç
local.contributor.kuauthorUyulur, Fırat
local.contributor.kuauthorÖnder, Tuğba Bağcı
local.contributor.kuauthorSyed, Hamzah
local.contributor.kuauthorLack, Nathan Alan
local.contributor.kuauthorÖnder, Tamer Tevfik
local.publication.orgunit1SCHOOL OF MEDICINE
local.publication.orgunit1GRADUATE SCHOOL OF HEALTH SCIENCES
local.publication.orgunit1Research Center
local.publication.orgunit2KUTTAM (Koç University Research Center for Translational Medicine)
local.publication.orgunit2School of Medicine
local.publication.orgunit2Graduate School of Health Sciences
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