/   Home   /   Newsroom   /   Research News

Scientists Find Epigenetic Regulation of Left-right Asymmetry by DNA Methylation

Sep 12, 2017     Email"> PrintText Size

DNA methylation is one of the major epigenetic modifications in vertebrates, which involves adding a methyl group to the 5th carbon of cytosine to form 5-methylcytosine (5mC), which is established and maintained by DNA methyltransferases (DNMT).

DNA methylation is associated with a number of key processes including transcription regulation, chromosome stability, genomic imprinting, and X-chromosome inactivation. Genome-wide 5mC mapping has implicated the role of DNA methylation during early embryogenesis. However, the precise role of DNA methylation in vertebrate development is still not fully understood.

Establishment of the three body axes (anterior-posterior, dorsal-ventral and left-right axes) is a critical step during animal development. Vertebrate body display external symmetry but the internal organs are positioned asymmetrically such as the heart, pancreas, liver and intestines having a defined position within the body cavity.

Left-Right asymmetry is first established by breaking symmetry, and then followed by laterality organ formation, where cilia generate directional fluid flow, which leads to asymmetric gene expression.

This asymmetric expression pattern then will direct internal organ primordium to position asymmetrically. However, very little is known about the role of DNA methylation in LR determination.

Using zebrafish as a model, the Hematopoiesis and Cardiovascular Development Group from Institute of Zoology of the Chinese Academy of Sciences, led by Prof. LIU Feng, found that loss of dnmt1 or dnmt3bb.1 disrupts laterality of organs including heart, pancreas, and liver.

Mechanistically, hypomethylation of the lefty2 gene enhancer caused by loss-of-dnmt1 can promote lefty2 expression, which in turn inhibits Nodal signaling, therefore leading to impaired DFC specification and loss of LR asymmetry.

In addition, Dnmt3bb.1 is required for cadherin 1 (cdh1)-mediated DFC clustering to ensure proper LR determination. This study unravels a new layer of regulation involving dynamic DNA methylation in embryonic development in vertebrates.

This study "Epigenetic regulation of left-right asymmetry by DNA methylation" was published in EMBO J online.

This work was supported by grants from the National Natural Science Foundation of China and the Ministry of Science and Technology of China.


Model for regulation of LR asymmetry by DNA methylation during embryogenesis in vertebrates In the presence of DNMTs, the expression of lefty2 and cdh1 is tightly controlled to ensure normal LR asymmetry; in the absence of DNMTs, the expression of lefty2 and cdh1 is dysregulated due to hypomethylation, thereby causing abnormal LR asymmetry. (Image by IOZ) 


(Editor: ZHANG Nannan)


LIU Feng

Institute of Zoology

E-mail: liuf@ioz.ac.cn

Related Articles

DNA methylation;RdDM;hybrid vigor

DNA Methylation Interaction Mediated by RdDM Not Involved in Hybrid Vigor

Jul 06, 2016

Hybrid vigor, or heterosis, is paramount trait for plant growth and crop breeding. Prof. ZHU Jiankang's lab at the Shanghai Center for Plant Stress Biology, Shanghai Institutes for Biological Sciences of Chinese Academy of Sciences developed a new epigenomic algorithm ide...

DNA methylation;methylation;castor bean

CHH Methylation Being Main Methylation form for Castor Bean Seeds

May 04, 2016

Prof. LIU Aizhong and his colleagues at the Kunming Institute of Botany (KIB) of Chinese Academy of Sciences comprehensively dissected the genomic DNA methylation in castor bean seeds. Unexpectedly, they discovered a novel genomic DNA methylation profile that the CHH meth...

Contact Us

Copyright © 2002 - Chinese Academy of Sciences