Asset Details
Do you wish to reserve the book?
EZH2 specifically regulates ISL1 during embryonic urinary tract formation
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
EZH2 specifically regulates ISL1 during embryonic urinary tract formation
Do you wish to request the book?
EZH2 specifically regulates ISL1 during embryonic urinary tract formation
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
EZH2 specifically regulates ISL1 during embryonic urinary tract formation
2024
Overview
Isl1
has been described as an embryonic master control gene expressed in the pericloacal mesenchyme. Deletion of
Isl1
from the genital mesenchyme in mice leads to an ectopic urethral opening and epispadias-like phenotype. Using genome wide association methods, we identified
ISL1
as the key susceptibility gene for classic bladder exstrophy (CBE), comprising epispadias and exstrophy of the urinary bladder. The most significant marker (rs6874700) identified in our recent GWAS meta-analysis achieved a
p
value of 1.48 × 10
− 24
within the
ISL1
region. In silico analysis of rs6874700 and all other genome-wide significant markers in Linkage Disequilibrium (LD) with rs6874700 (D’ = 1.0; R
2
> 0.90) revealed marker rs2303751 (
p
value 8.12 × 10
− 20
) as the marker with the highest regulatory effect predicted. Here, we describe a novel 1.2 kb intragenic promoter residing between 6.2 and 7.4 kb downstream of the
ISL1
transcription starting site, which is located in the reverse DNA strand and harbors a binding site for EZH2 at the exact region of marker rs2303751. We show, that EZH2 silencing in HEK cells reduces
ISL1
expression. We show that
ezh2
−/−
knockout (KO) zebrafish larvae display tissues specificity of ISL1 regulation with reduced expression of Isl1 in the pronephric region of zebrafish larvae. In addition, a shorter and malformed nephric duct is observed in
ezh2
−/−
ko zebrafish
Tg(wt1ß:eGFP)
reporter lines. Our study shows, that Ezh2 is a key regulator of
Isl1
during urinary tract formation and suggests tissue specific
ISL1
dysregulation as an underlying mechanism for CBE formation.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 631/208
/ Animals
/ Bladder Exstrophy - genetics
/ Bladder Exstrophy - metabolism
/ Embryos
/ Enhancer of Zeste Homolog 2 Protein - genetics
/ Enhancer of Zeste Homolog 2 Protein - metabolism
/ EZH2
/ Gene Expression Regulation, Developmental
/ Genome-Wide Association Study
/ Genomes
/ HEK293
/ Humanities and Social Sciences
/ Humans
/ ISL1
/ Larvae
/ LIM-Homeodomain Proteins - genetics
/ LIM-Homeodomain Proteins - metabolism
/ Promoter
/ Science
/ Transcription Factors - genetics
/ Transcription Factors - metabolism
