Genome-wide profiling of gene expression and DNA methylation provides insight into low-altitude acclimation in Tibetan pigs

Jin, Long; Mao, Ke; Li, Jing; Huang, Wenyao; Che, Tiandong; Fu, Yuhua; Tang, Qianzi; Liu, Pengliang; Yang, Song; Li, Rui; Lin, Xuxu; Shang, Dazhi; Liu, Yihui; Liu, Yingkai; Ma, Jideng; Gu, Yiren; Li, Xuewei; Li, Mingzhou

doi:10.1016/j.gene.2017.11.074

Cited by 17 publications

(12 citation statements)

References 76 publications

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“…For most of these tissues, we found the mtDNA copy number of high-altitude animals were lower than low-altitude counterparts. The result is consistent with the previous observations of decreased mitochondrial content with a concurrent smaller production of reactive oxygen species (ROS) across the vertebrate animal tissues, both in vitro and in vivo, when exposed to chronic hypoxia (Zhang et al 2008;Heather et al 2012;Li Y et al 2016;Niu et al 2017;Jin et al 2018). However, increase in mitochondrial density occur in the early phases of acclimatization in response to acute hypoxia, which increases the metabolic cost of oxygen at the expense of cell damage by harmful Figure 2.…”

Section: Detection Of Mtdna Copy Numbersupporting

confidence: 91%

Analysis of mitochondrial DNA sequence and copy number variation across five high-altitude species and their low-altitude relatives

Liu

Jin

Long

et al. 2018

Mitochondrial DNA Part B

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High-altitude inhospitable environments impose a formidable life challenge for the local animals. Training and exposure to high-altitude environments produce both distinct physiological and phenotypic characteristics. The mitochondrion, an organelle crucial for the energy production, plays an important role in hypoxia adaptation. In this study, we investigated the mitochondrial DNA (mtDNA) polymorphism and copy number variation between the population pairs from distinct altitudes across the multi-species. Higher mitochondrial DNA control region's genetic diversity is conspicuous in highaltitude animals versus low-altitude relatives. We also found an accordant decrease of mtDNA copy number in most of the tissues from high-altitude animals. Compared to mammals, chickens have significantly distinct mitogenomic characteristics, and more significant changes in the skeletal muscle mtDNA copy number between high-and low-altitude individuals. Our study catches a snapshot of the biological similarities and differences in the mitochondrial high-altitude acclimation across the species.

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Section: Detection Of Mtdna Copy Numbersupporting

confidence: 91%

Analysis of mitochondrial DNA sequence and copy number variation across five high-altitude species and their low-altitude relatives

Liu

Jin

Long

et al. 2018

Mitochondrial DNA Part B

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“…The calcium channel, voltage-dependent, gamma subunit 6 (CACNG6) gene encodes a protein that stabilizes the calcium channel [22]. Recent studies have revealed negative relations of CACNG6 gene expression to chronic obstructive pulmonary disease, responses of the human airway epithelium following injury and parenchyma in lung tissues [23].…”

Section: R E T R a C T E D A R T I C L Ementioning

confidence: 99%

RETRACTED ARTICLE: Inhibition of miR-296-5p protects the heart from cardiac hypertrophy by targeting CACNG6

Wang

Liu

et al. 2019

Gene Ther

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Heart often undergoes mal-remodeling and hypertrophic growth in response to pathological stress. MiRNAs can regulate the cardiac function and participate in the regulation of cardiac hypertrophy. The present study aims at identifying the role of miR-296-5p in cardiac hypertrophy and further the underlying mechanism in hypertrophic cascades. Mice with cardiac hypertrophy were established by transverse aortic constriction (TAC). Cardiac hypertrophy in cardiomyocytes was induced by angiotensin II. Expression of miR-296-5p and its target gene CACNG6 was examined in cardiomyocytes transfected by miRNA. The expression of miR-296-5p was upregulated in mice with TAC surgery. The inhibition of miR-296-5p attenuated cardiac hypertrophy both in vitro and in vivo. And dual-luciferase reporter assays showed CACNG6 was the direct target of miR-296-5p, which modulated the expression of calcium signaling. MiR-296-5p was found to aggravate cardiac hypertrophy by targeting CACNG6, which suggests inhibition of miR-296-5p might have clinical potential to suppress cardiac hypertrophy and heart failure.

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“…Tibetan pigs inhabit the Tibetan Plateau and have a well-developed heart, which is better adapted to hypoxia than that of lowland pigs [21, 22]. A number of rapidly evolving and positively selected genes have been reported for Tibetan pigs based on high-throughput sequencing [23–27], and several important candidate genes for high-altitude adaptation, including genes involved in angiogenesis, ATP binding, and glucose metabolic processes as well as important pathways such as the hypoxia-inducible factor 1 (HIF-1) signaling pathway, have been revealed by comparative transcriptomic and proteomic analyses of Tibetan pig heart tissues [28]. However, the mechanisms involved in the regulation of gene expression at high altitude remain unclear.…”

Section: Introductionmentioning

confidence: 99%

Genome-wide DNA methylation profiles in Tibetan and Yorkshire pigs under high-altitude hypoxia

Zhang

Ban

Gou

et al. 2019

J Animal Sci Biotechnol

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Background Tibetan pigs, which inhabit the Tibetan Plateau, exhibit distinct phenotypic and physiological characteristics from those of lowland pigs and have adapted well to the extreme conditions at high altitude. However, the genetic and epigenetic mechanisms of hypoxic adaptation in animals remain unclear. Methods Whole-genome DNA methylation data were generated for heart tissues of Tibetan pigs grown in the highland (TH, n = 4) and lowland (TL, n = 4), as well as Yorkshire pigs grown in the highland (YH, n = 4) and lowland (YL, n = 4), using methylated DNA immunoprecipitation sequencing. Results We obtained 480 million reads and detected 280679, 287224, 259066, and 332078 methylation enrichment peaks in TH, YH, TL, and YL, respectively. Pairwise TH vs. YH, TL vs. YL, TH vs. TL, and YH vs. YL comparisons revealed 6829, 11997, 2828, and 1286 differentially methylated regions (DMRs), respectively. These DMRs contained 384, 619, 192, and 92 differentially methylated genes (DMGs), respectively. DMGs that were enriched in the hypoxia-inducible factor 1 signaling pathway and pathways involved in cancer and hypoxia-related processes were considered to be important candidate genes for high-altitude adaptation in Tibetan pigs. Conclusions This study elucidates the molecular and epigenetic mechanisms involved in hypoxic adaptation in pigs and may help further understand human hypoxia-related diseases. Electronic supplementary material The online version of this article (10.1186/s40104-019-0316-y) contains supplementary material, which is available to authorized users.

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Genome-wide profiling of gene expression and DNA methylation provides insight into low-altitude acclimation in Tibetan pigs

Cited by 17 publications

References 76 publications

Analysis of mitochondrial DNA sequence and copy number variation across five high-altitude species and their low-altitude relatives

Analysis of mitochondrial DNA sequence and copy number variation across five high-altitude species and their low-altitude relatives

RETRACTED ARTICLE: Inhibition of miR-296-5p protects the heart from cardiac hypertrophy by targeting CACNG6

Genome-wide DNA methylation profiles in Tibetan and Yorkshire pigs under high-altitude hypoxia

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