A CRISPR-Cas9 screen identifies essential CTCF anchor sites for estrogen receptor-driven breast cancer cell proliferation.

Nucleic Acids Research
Gozde KorkmazReuven Agami

Abstract

Estrogen receptor α (ERα) is an enhancer activating transcription factor, a key driver of breast cancer and a main target for cancer therapy. ERα-mediated gene regulation requires proper chromatin-conformation to facilitate interactions between ERα-bound enhancers and their target promoters. A major determinant of chromatin structure is the CCCTC-binding factor (CTCF), that dimerizes and together with cohesin stabilizes chromatin loops and forms the boundaries of topologically associated domains. However, whether CTCF-binding elements (CBEs) are essential for ERα-driven cell proliferation is unknown. To address this question in a global manner, we implemented a CRISPR-based functional genetic screen targeting CBEs located in the vicinity of ERα-bound enhancers. We identified four functional CBEs and demonstrated the role of one of them in inducing chromatin conformation changes in favor of activation of PREX1, a key ERα target gene in breast cancer. Indeed, high PREX1 expression is a bona-fide marker of ERα-dependency in cell lines, and is associated with good outcome after anti-hormonal treatment. Altogether, our data show that distinct CTCF-mediated chromatin structures are required for ERα- driven breast cancer cell prolifer...Continue Reading

References

May 20, 2000·Journal of Mammary Gland Biology and Neoplasia·R G LapidusN E Davidson
May 25, 2006·Annual Review of Genomics and Human Genetics·Glenn A MastonMichael R Green
Oct 3, 2006·Nature Genetics·Jason S CarrollMyles Brown
Nov 30, 2006·Pharmacological Reviews·Karin Dahlman-WrightJan-Ake Gustafsson
Jan 11, 2007·Molecular and Cellular Biology·Igor ChernukhinElena Klenova
Sep 19, 2008·Genome Biology·Yong ZhangX Shirley Liu
Nov 1, 2008·Cancer Research·Chang S Chan, Jun S Song
Mar 12, 2009·Methods : a Companion to Methods in Enzymology·Dominic SchmidtDuncan T Odom
May 30, 2009·Molecular Endocrinology·Wilbert ZwartRob Michalides
Nov 6, 2009·Nature·Melissa J FullwoodYijun Ruan
Dec 23, 2009·Developmental Biology·Michael Bulger, Mark Groudine
Jan 30, 2010·Bioinformatics·Aaron R Quinlan, Ira M Hall
May 6, 2010·Nature Reviews. Genetics·Jesse R Raab, Rohinton T Kamakaka
Jul 9, 2010·The Journal of Biological Chemistry·Yu ZhangYongfeng Shang
Sep 14, 2010·Current Biology : CB·Mike Levine
Dec 22, 2010·Molecular Cell·Maria Soledad SosaMarcelo G Kazanietz
Dec 7, 2011·BMC Genomics·Caryn S Ross-InnesJason S Carroll
Jun 19, 2012·Annual Review of Genomics and Human Genetics·Glenn A MastonMichael R Green
Sep 8, 2012·Nature·UNKNOWN ENCODE Project Consortium
Sep 11, 2012·Nature Methods·Harmen J G van de WerkenWouter de Laat
Mar 12, 2013·Molecular Cell·Johan H Gibcus, Job Dekker
Mar 19, 2013·Cell·Matthias Merkenschlager, Duncan T Odom
May 3, 2013·Genome Research·Nasun HahW Lee Kraus
May 28, 2013·Cell·Jennifer E Phillips-CreminsVictor G Corces
Jun 19, 2013·Nature Biotechnology·Vibhor KumarShyam Prabhakar
Nov 5, 2013·Nature Genetics·Weiyi ToySarat Chandarlapaty
Dec 18, 2013·Science·Tim WangEric S Lander
Dec 18, 2013·Science·Ophir ShalemFeng Zhang

❮ Previous
Next ❯

Citations

Dec 31, 2019·Cell Cycle·Guergana Tchakarska, Brigitte Sola
Jun 28, 2020·Hormones & Cancer·David K LungElaine T Alarid
Oct 25, 2020·Proceedings of the National Academy of Sciences of the United States of America·Nuthasuda SrijakotreChristina A Mitchell
Dec 8, 2020·Endocrinology·Anca M FarcasJason S Carroll

Jan 11, 2021·Bulletin du cancer·Andrey KleshninStéphan Vagner
Apr 30, 2021·Development·Ersin AkinciRichard I Sherwood

❮ Previous
Next ❯

Methods Mentioned

BETA
transfection
PCR
flow cytometry
HTseq
immunoprecipitation
ChIP
ChIPseq
RNA-seq
ChIP-seq
DNA-seq

Software Mentioned

MACS
ENCODE
FIMO
bowtie2
peakC
dREG Regulatory Element detection from GRO - seq ( dREG )
DRIVE
MEME
seaborn
FlowJo

Related Concepts

Related Feeds

CRISPR (general)

Clustered regularly interspaced short palindromic repeats (CRISPR) are DNA sequences in the genome that are recognized and cleaved by CRISPR-associated proteins (Cas). CRISPR-Cas system enables the editing of genes to create or correct mutations. Discover the latest research on CRISPR here.

CRISPR for Genome Editing

Genome editing technologies enable the editing of genes to create or correct mutations. Clustered regularly interspaced short palindromic repeats (CRISPR) are DNA sequences in the genome that are recognized and cleaved by CRISPR-associated proteins (Cas). Here is the latest research on the use of CRISPR-Cas system in gene editing.

Breast Cancer: Therapeutic Approaches

Several different therapeutic approaches are used to treat breast cancer. These include chemotherapy, hormonal therapy, targeted therapy, and Immunotherapy. Discover the latest research on breast cancer therapeutic approaches here.

Related Papers

Current Opinion in Genetics & Development
Tamer AliMarek Bartkuhn
Cold Spring Harbor Symposia on Quantitative Biology
Joanna Achinger-KaweckaSusan J Clark
© 2021 Meta ULC. All rights reserved