Setd5 is Required in Cardiopharyngeal Mesoderm for Heart Development and Its Haploinsufficiency is Associated with Outflow Tract Defects in Mouse

Overview

Journal Genesis

Specialties Biology
Molecular Biology

Date 2021 May 29

PMID 34050709

Citations 6

Authors

Michelle Yu-Qing Cheung

Catherine Roberts

Peter Scambler

Athanasia Stathopoulou

Affiliations

Soon will be listed here.

Abstract

Congenital heart defects are a feature of several genetic haploinsufficiency syndromes, often involving transcriptional regulators. One property of haploinsufficient genes is their propensity for network interactions at the gene or protein level. In this article we took advantage of an online dataset of high throughput screening of mutations that are embryonic lethal in mice. Our aim was to identify new genes where the loss of function caused cardiovascular phenotypes resembling the 22q11.2 deletion syndrome models, that is, heterozygous and homozygous loss of Tbx1. One gene with a potentially haploinsufficient phenotype was identified, Setd5, thought to be involved in chromatin modification. We found murine Setd5 haploinsufficiency to be associated with double outlet right ventricle and perimembranous ventricular septal defect, although no genetic interaction with Tbx1 was detected. Conditional mutagenesis revealed that Setd5 was required in cardiopharyngeal mesoderm for progression of the heart tube through the ballooning stage to create a four-chambered heart.

Citing Articles

Molecular convergence of risk variants for congenital heart defects leveraging a regulatory map of the human fetal heart.

Ma X, Conley S, Kosicki M, Bredikhin D, Cui R, Tran S medRxiv. 2024; .

PMID: 39606363 PMC: 11601760. DOI: 10.1101/2024.11.20.24317557.

Defining Biological and Biochemical Functions of Noncanonical SET Domain Proteins.

Sun W, Justice I, Green E J Mol Biol. 2023; 436(7):168318.

PMID: 37863247 PMC: 10957327. DOI: 10.1016/j.jmb.2023.168318.

Protein posttranslational modifications in health and diseases: Functions, regulatory mechanisms, and therapeutic implications.

Zhong Q, Xiao X, Qiu Y, Xu Z, Chen C, Chong B MedComm (2020). 2023; 4(3):e261.

PMID: 37143582 PMC: 10152985. DOI: 10.1002/mco2.261.

Structure, activity and function of the lysine methyltransferase SETD5.

Li M, Hou Y, Zhang Z, Zhang B, Huang T, Sun A Front Endocrinol (Lausanne). 2023; 14:1089527.

PMID: 36875494 PMC: 9982096. DOI: 10.3389/fendo.2023.1089527.

Neurobehavioral characteristics of mice with mutations as models of IDD23 and KBG syndromes.

Nakagawa T, Hattori S, Hosoi T, Nakayama K Front Genet. 2023; 13:1022339.

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