Comparison Of Methylome And Transcriptome Between Chicken Hearts Of Low-and High-altitude

Tibetan chickens are highly adaptable to extreme high-altitude environments and have shown good performance in survival and reproduction.Unlike low altitude chickens,Tibetan chickens have several physiological parameters that effectively promote blood oxygen-carrying capacity,such as larger organs（heart,liver,and lungs）,lower arterial oxygen partial pressure,lower venous blood p H,higher High venous CO₂partial pressure,and higher hemoglobin concentration.With the development of science and technology,more and more researchers have begun to pay attention to the epigenetic regulation mechanism of chickens at high and low altitudes,and the interaction between DNA methylation and m RNAs is particularly worthy of attention.This study aims to investigate the cardiac DNA methylation profiles and transcriptome expression profiles of Tibetan chickens in high-altitude environments and plain chickens in low-altitude environments.We established a synergistic regulatory network for epigenetic modification,and jointly analyzed differentially methylated genes and differentially expressed genes to deeply explore how Tibetan chickens adapt to high-altitude environments,and to study its molecular mechanisms and physiological functions,so as to contribute to the development of plateau animal husbandry.The main research results are as follows:（1）Using high-throughput sequencing technology to sequence the transcriptomes of the heart tissues of 6 high-and low-altitude chickens,a total of 1221 differentially expressed genes were obtained,of which 377 genes were up-regulated and 844 genes were down-regulated in Tibetan chickens.We conducted signal pathway and functional enrichment analysis and found that the differentially expressed genes in the heart tissues of the two breeds of chickens were mainly enriched in biological processes and signals such as the regulation of vascular development,the regulation of active oxygen metabolism,the regulation of myocardial contraction,and the regulation of hematopoiesis.path.（2）Genome-wide methylation sequencing data with a depth of no less than 22×was performed on each heart tissue sample,and 983 differentially methylated genes were obtained at the promoter CG site.Further analysis of these genes found that they were mainly involved in oxidoreductase activity,metabolic pathways,cytokine-cytokine receptor interaction,MAPK signaling pathway,endocytosis,cellular senescence,neuroactive ligand-receptor interaction,necrosis Biological processes such as apoptosis.These results highlight differences in the adaptation of chickens at high and low altitudes to different environmental conditions.（3）Through the integrated analysis of DEGs obtained by transcriptome sequencing and DMGs obtained by methylation sequencing analysis,a total of 37 genes,including COL19A1 and RUNX1,which were negatively correlated with the degree of methylation and expression,were obtained.These genes are mainly involved in biological processes such as proliferation,differentiation and maturation of cardiomyocytes,and play a key regulatory role in the formation and maintenance of the structure and function of the heart under hypoxic conditions.（4）Chicken embryonic cardiomyocytes were successfully isolated for purification and culture,and a cardiomyocyte hypoxia model was constructed to simulate plateau hypoxia environment to verify the expression of key differential genes（COL19A1,NCKAP1L,CDC45,RUNX3）in the joint analysis.The model used in this experiment can be used to study the hypoxia adaptability of cardiomyocytes,which will provide new ideas for animal altitude sickness and its corresponding anti-hypoxic molecular breeding.