Dataset Information

Genome-wide studies reveal the essential and opposite roles of ARID1A in controlling human cardiogenesis and neurogenesis from pluripotent stem cells.

ABSTRACT: BACKGROUND:Early human heart and brain development simultaneously occur during embryogenesis. Notably, in human newborns, congenital heart defects strongly associate with neurodevelopmental abnormalities, suggesting a common gene or complex underlying both cardiogenesis and neurogenesis. However, due to lack of in vivo studies, the molecular mechanisms that govern both early human heart and brain development remain elusive. RESULTS:Here, we report ARID1A, a DNA-binding subunit of the SWI/SNF epigenetic complex, controls both neurogenesis and cardiogenesis from human embryonic stem cells (hESCs) through distinct mechanisms. Knockout-of-ARID1A (ARID1A-/-) leads to spontaneous differentiation of neural cells together with globally enhanced expression of neurogenic genes in undifferentiated hESCs. Additionally, when compared with WT hESCs, cardiac differentiation from ARID1A -/- hESCs is prominently suppressed, whereas neural differentiation is significantly promoted. Whole genome-wide scRNA-seq, ATAC-seq, and ChIP-seq analyses reveal that ARID1A is required to open chromatin accessibility on promoters of essential cardiogenic genes, and temporally associated with key cardiogenic transcriptional factors T and MEF2C during early cardiac development. However, during early neural development, transcription of most essential neurogenic genes is dependent on ARID1A, which can interact with a known neural restrictive silencer factor REST/NRSF. CONCLUSIONS:We uncover the opposite roles by ARID1A to govern both early cardiac and neural development from pluripotent stem cells. Global chromatin accessibility on cardiogenic genes is dependent on ARID1A, whereas transcriptional activity of neurogenic genes is under control by ARID1A, possibly through ARID1A-REST/NRSF interaction.

SUBMITTER: Liu J

PROVIDER: S-EPMC7350744 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Genome-wide studies reveal the essential and opposite roles of ARID1A in controlling human cardiogenesis and neurogenesis from pluripotent stem cells.

Liu Juli J Liu Sheng S Gao Hongyu H Han Lei L Chu Xiaona X Sheng Yi Y Shou Weinian W Wang Yue Y Liu Yunlong Y Wan Jun J Yang Lei L

Genome biology 20200709 1

<h4>Background</h4>Early human heart and brain development simultaneously occur during embryogenesis. Notably, in human newborns, congenital heart defects strongly associate with neurodevelopmental abnormalities, suggesting a common gene or complex underlying both cardiogenesis and neurogenesis. However, due to lack of in vivo studies, the molecular mechanisms that govern both early human heart and brain development remain elusive.<h4>Results</h4>Here, we report ARID1A, a DNA-binding subunit of ...[more]

PMID: 32646524

Similar Datasets

Project description:Polyamines (PAs) play a critical role in growth and developmental processes and stress responses in plants. Polyamine oxidase (PAO) is a flavin adenine dinucleotide (FAD)-dependent enzyme that plays a major role in PA catabolism. Here, for the first time, PAO genes in maize were screened for the whole genome-wide and nine ZmPAO genes were identified in this study, named as ZmPAO1-9. Based on structural characteristics and a comparison of phylogenetic relationships of PAO gene families from seven representative species, all nine PAO proteins in maize were categorized into three distinct subfamilies. Further, chromosome location and schematic structure revealed an unevenly distribution on chromosomes and evolutionarily conserved structure features of ZmPAO genes in maize, respectively. Furthermore, transcriptome analysis demonstrated that ZmPAO genes showed differential expression patterns at diverse developmental stages of maize, suggesting that these genes may play functional developmental roles in multiple tissues. Further, through qRT-PCR validation, these genes were confirmed to be responsive to heat, drought and salinity stress treatments in three various tissues, indicating their potential roles in abiotic stress responses. Eventually, to verify the biological function of ZmPAO genes, the transgenic Arabidopsis plants overexpressing ZmPAO6 gene were constructed as a typical representative to explore functional roles in plants. The results demonstrated that overexpression of ZmPAO6 can confer enhanced heat tolerance through mediating polyamine catabolism in transgenic Arabidopsis, which might result in reduced H2O2 and MDA accumulation and alleviated chlorophyll degradation under heat stress treatment, indicating that ZmPAO6 may play a crucial role in enhancing heat tolerance of transgenic Arabidopsis through the involvement in various physiological processes. Further, the expression analysis of related genes of antioxidant enzymes including glutathione peroxidase (GPX) and ascorbate peroxidase (APX) demonstrated that ZmPAO6 can enhance heat resistance in transgenic Arabidopsis through modulating heat-induced H2O2 accumulation in polyamine catabolism. Taken together, our results are the first to report the ZmPAO6 gene response to heat stress in plants and will serve to present an important theoretical basis for further unraveling the function and regulatory mechanism of ZmPAO genes in growth, development and adaptation to abiotic stresses in maize.

Dataset Information

Genome-wide studies reveal the essential and opposite roles of ARID1A in controlling human cardiogenesis and neurogenesis from pluripotent stem cells.

Publications

Genome-wide studies reveal the essential and opposite roles of ARID1A in controlling human cardiogenesis and neurogenesis from pluripotent stem cells.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets