Endogenous HIF2A reporter systems for high-throughput functional screening

M. Nazhif Zaini, Saroor A. Patel, Saiful Effendi Syafruddin, Paulo Rodrigues, Sakari Vanharanta

Research output: Contribution to journalArticle

Abstract

Tissue-specific transcriptional programs control most biological phenotypes, including disease states such as cancer. However, the molecular details underlying transcriptional specificity is largely unknown, hindering the development of therapeutic approaches. Here, we describe novel experimental reporter systems that allow interrogation of the endogenous expression of HIF2A, a critical driver of renal oncogenesis. Using a focused CRISPR-Cas9 library targeting chromatin regulators, we provide evidence that these reporter systems are compatible with high-throughput screening. Our data also suggests redundancy in the control of cancer type-specific transcriptional traits. Reporter systems such as those described here could facilitate large-scale mechanistic dissection of transcriptional programmes underlying cancer phenotypes, thus paving the way for novel therapeutic approaches.

Original languageEnglish
Article number12063
JournalScientific Reports
Volume8
Issue number1
DOIs
Publication statusPublished - 1 Dec 2018

Fingerprint

Clustered Regularly Interspaced Short Palindromic Repeats
Phenotype
Neoplasms
Libraries
Chromatin
Dissection
Carcinogenesis
Kidney
Therapeutics

ASJC Scopus subject areas

  • General

Cite this

Endogenous HIF2A reporter systems for high-throughput functional screening. / Zaini, M. Nazhif; Patel, Saroor A.; Syafruddin, Saiful Effendi; Rodrigues, Paulo; Vanharanta, Sakari.

In: Scientific Reports, Vol. 8, No. 1, 12063, 01.12.2018.

Research output: Contribution to journalArticle

Zaini, M. Nazhif ; Patel, Saroor A. ; Syafruddin, Saiful Effendi ; Rodrigues, Paulo ; Vanharanta, Sakari. / Endogenous HIF2A reporter systems for high-throughput functional screening. In: Scientific Reports. 2018 ; Vol. 8, No. 1.
@article{9579b09119e34e079a7a965143e52d8e,
title = "Endogenous HIF2A reporter systems for high-throughput functional screening",
abstract = "Tissue-specific transcriptional programs control most biological phenotypes, including disease states such as cancer. However, the molecular details underlying transcriptional specificity is largely unknown, hindering the development of therapeutic approaches. Here, we describe novel experimental reporter systems that allow interrogation of the endogenous expression of HIF2A, a critical driver of renal oncogenesis. Using a focused CRISPR-Cas9 library targeting chromatin regulators, we provide evidence that these reporter systems are compatible with high-throughput screening. Our data also suggests redundancy in the control of cancer type-specific transcriptional traits. Reporter systems such as those described here could facilitate large-scale mechanistic dissection of transcriptional programmes underlying cancer phenotypes, thus paving the way for novel therapeutic approaches.",
author = "Zaini, {M. Nazhif} and Patel, {Saroor A.} and Syafruddin, {Saiful Effendi} and Paulo Rodrigues and Sakari Vanharanta",
year = "2018",
month = "12",
day = "1",
doi = "10.1038/s41598-018-30499-2",
language = "English",
volume = "8",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",

}

TY - JOUR

T1 - Endogenous HIF2A reporter systems for high-throughput functional screening

AU - Zaini, M. Nazhif

AU - Patel, Saroor A.

AU - Syafruddin, Saiful Effendi

AU - Rodrigues, Paulo

AU - Vanharanta, Sakari

PY - 2018/12/1

Y1 - 2018/12/1

N2 - Tissue-specific transcriptional programs control most biological phenotypes, including disease states such as cancer. However, the molecular details underlying transcriptional specificity is largely unknown, hindering the development of therapeutic approaches. Here, we describe novel experimental reporter systems that allow interrogation of the endogenous expression of HIF2A, a critical driver of renal oncogenesis. Using a focused CRISPR-Cas9 library targeting chromatin regulators, we provide evidence that these reporter systems are compatible with high-throughput screening. Our data also suggests redundancy in the control of cancer type-specific transcriptional traits. Reporter systems such as those described here could facilitate large-scale mechanistic dissection of transcriptional programmes underlying cancer phenotypes, thus paving the way for novel therapeutic approaches.

AB - Tissue-specific transcriptional programs control most biological phenotypes, including disease states such as cancer. However, the molecular details underlying transcriptional specificity is largely unknown, hindering the development of therapeutic approaches. Here, we describe novel experimental reporter systems that allow interrogation of the endogenous expression of HIF2A, a critical driver of renal oncogenesis. Using a focused CRISPR-Cas9 library targeting chromatin regulators, we provide evidence that these reporter systems are compatible with high-throughput screening. Our data also suggests redundancy in the control of cancer type-specific transcriptional traits. Reporter systems such as those described here could facilitate large-scale mechanistic dissection of transcriptional programmes underlying cancer phenotypes, thus paving the way for novel therapeutic approaches.

UR - http://www.scopus.com/inward/record.url?scp=85051473955&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85051473955&partnerID=8YFLogxK

U2 - 10.1038/s41598-018-30499-2

DO - 10.1038/s41598-018-30499-2

M3 - Article

VL - 8

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

IS - 1

M1 - 12063

ER -