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Critical roles of CHD7 during mouse cardiogenesis

CHD7 在小鼠心脏发生过程中的关键作用

基本信息

批准号：
10625572
负责人：
KAI JIAO
金额：
$ 14.82万
依托单位：
AUGUSTA UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-05-23 至 2024-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10625572
关键词：
Critical roles CHD7 during mouse

项目摘要

Abstract: CHARGE syndrome (Coloboma of the eye, Heart defects, Atresia of the choanae, Retardation of growth/development, Genital abnormalities and Ear anomalies) is a severe developmental disorder affecting multiple organs. Congenital heart diseases are major clinical features of CHARGE syndrome, affecting >75% of patients. More than 70% of all CHARGE cases are caused by the haploinsufficiency of CHD7, a gene that encodes an ATP-dependent chromatin remodeling factor. The major goal of this project is to reveal the functions of CHD7 during heart development and therefore provide mechanistic insights into the birth defects caused by mutations in CHD7. We recently identified CHD7 as an embryonic heart interaction partner of SMADs1, 5, and 8 (SMADs1/5/8), which are BMP receptor-activated SMADs. We further showed that CHD7 is required for normal expression of Nkx2.5, a core cardiogenic transcription factor downstream of BMP signaling. Thus, our study provided the first evidence implicating CHD7 as a direct epigenetic regulator of cardiogenic genes. Currently, the functions and molecular activities of CHD7 during heart development remain largely elusive, presenting a major barrier for understanding the developmental basis for the heart defects in CHARGE patients. We hypothesize that CHD7 regulates the epigenetic architecture of crucial cardiogenic genes to promote normal heart development in mammals. Two specific aims are proposed to test this hypothesis. In the 1st aim, we will reveal the regulatory target network of CHD7 in cardiomyocytes derived from the second heart field (SHF) and examine how CHD7 is specifically loaded onto its target sites. In the 2nd aim, we will test the role of CHD7 in recruiting histone methyltransferase to promote methylation of histone H3 lysine 4 at its associated enhancers. Accomplishing the proposed studies will not only greatly advance our knowledge of the tissular-, cellular- and molecular- activities of CHD7 in developing hearts, but also will provide us with crucial clues regarding how an epigenetic regulator acts coordinately with other genetic/epigenetic regulators to promote normal cardiogenesis in mammals. Information obtained from our research will be invaluable for understanding the mechanisms underlying the heart defects observed in CHARGE syndrome patients.

文摘:

项目成果

期刊论文数量（19）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Myocardial Mycn is essential for mouse ventricular wall morphogenesis.

DOI：
10.1016/j.ydbio.2012.10.005
发表时间：
2013-01-01
期刊：
Developmental biology
影响因子：
2.7
作者：
Harmelink C;Peng Y;DeBenedittis P;Chen H;Shou W;Jiao K
通讯作者：
Jiao K

Functions of miRNAs during Mammalian Heart Development.

DOI：
10.3390/ijms17050789
发表时间：
2016-05-21
期刊：
International journal of molecular sciences
影响因子：
5.6
作者：
Yan S;Jiao K
通讯作者：
Jiao K

Cell autonomous requirement of endocardial Smad4 during atrioventricular cushion development in mouse embryos.

DOI：
10.1002/dvdy.22493
发表时间：
2011-01
期刊：
DEVELOPMENTAL DYNAMICS
影响因子：
2.5
作者：
Song, Langying;Zhao, Mei;Wu, Bingruo;Zhou, Bin;Wang, Qin;Jiao, Kai
通讯作者：
Jiao, Kai

CHD7 regulates cardiovascular development through ATP-dependent and -independent activities.

CHD7 通过 ATP 依赖性和非依赖性活动调节心血管发育。

DOI：
10.1073/pnas.2005222117
发表时间：
2020
期刊：
Proceedings of the National Academy of Sciences of the United States of America
影响因子：
11.1
作者：
Yan,Shun;Thienthanasit,Rassarin;Chen,Dongquan;Engelen,Erik;Brühl,Joanna;Crossman,DavidK;Kesterson,Robert;Wang,Qin;Bouazoune,Karim;Jiao,Kai
通讯作者：
Jiao,Kai

Disruption of PCP signaling causes limb morphogenesis and skeletal defects and may underlie Robinow syndrome and brachydactyly type B.