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Integrated analysis of the methylome and transcriptome of chickens with fatty liver hemorrhagic syndrome


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- Integrated analysis of the methylome and transcriptome of chickens with fatty liver hemorrhagic syndrome.
- Fatty liver hemorrhagic syndrome (FLHS) is a serious disease and is tightly linked to lipid homeostasis.
- Keywords: DNA methylation, RNA-seq, Fatty liver hemorrhagic syndrome, Lipid metabolism, Cellular junction and communication.
- For chickens, fatty liver hemorrhagic syndrome (FLHS) is a serious disease, which is characterized by massive lipid accretion and hemorrhagic spots of the liver [1]..
- physiological characteristics of FLHS are quite different from common fatty liver syndrome (FLS).
- In particular, DNA methylation, an important epigenetic modification, has been closely associated with hepatic lipogenesis and fatty liver [12, 13].
- Previous reports have demonstrated lipid metabolism to be up-regulated with differential gene methylation in in- dividuals with fatty liver disease [15].
- Liu et al.
- Sookoian et al.
- demonstrated hyper methylation of PPARγ in fatty liver subjects [17]..
- In previous study, Zhang et al.
- Overt lower genome-wide methylation levels were detected in the fatty liver group (Fig.
- 1 Global methylation pattern in normal and liver and fatty liver.
- Tan et al.
- In previous studies, we reported an induction method and reproduction mode by which to generate a fatty liver chicken line [3].
- For successive generations of the line, fatty liver becomes less severe and presents only hepato- cyte steatosis rather than a hemorrhagic phenotype.
- c The methylation levels of all genes with different transcriptional levels in gene body, up- and down-stream in fatty liver group.
- DNA methylation analysis is a common approach and has been shown to play a crucial role in the development of fatty liver [19].
- This is consistent with our findings, and suggests that distinct characteristics of the methylome may be useful for diag- nosing fatty liver..
- In fatty liver chickens, pathways of lipogen- esis were found to be substantially elevated, with similar alterations of both methylation and expression as previ- ously reported [16, 26].
- Kim et al..
- reported a negative correlation between DNA methyla- tion and gene expression of APOA4 in fatty liver individ- uals [28], which is consistent with our results.
- Hong et al.
- demonstrated PRKG1 to be hypo-methylated and increasingly expressed in a fatty liver model induced with oleic acid [29].
- et al.
- demonstrated ITPR1 specific knock-out mice could reverse fatty liver [30], although methylation data were not provided.
- Manuel et al.
- demonstrated that impaired intercellular communication and gap junc- tion were involved in the fatty liver pathological process, with gap junction playing a protective role by mainten- ance of homeostasis through cell-to-cell communication [31].
- The PPAR signaling pathway is widely regarded as a hub target for lipid metabolism, the inhibition of which could dampen hepatic fat accumulation, relieving fatty liver [33].
- found hyper-methylation of PPARγ in fatty liver subjects [17], which suggests a methylation regulatory target for FLHS.
- The fatty liver susceptible line and control line of Jingxing-Huang chicken were used for experiments [3]..
- Briefly, for the fatty liver susceptible line, the initial Jingxing-Huang chickens (F0 generation) were induced by a high-fat diet, while the chickens were fed a basal diet for control line.
- In F1 generation, male chickens with FLHS in the fatty liver group and non-FLHS chickens in the control group were assessed.
- Apparent feature of fatty liver and normal liver.
- (a) Phenotype of fatty liver.
- Global methylation pattern (mCHG and mCHH) in fatty liver and normal liver.
- (a-b) The methylation level with spe- cific site mCHG and mCHH of all genes grouped by transcriptional level in fatty liver group.
- FLHS: Fatty liver hemorrhagic syndrome.
- FLS: Fatty liver syndrome;.
- The data that support the findings in this study are available from corresponding author with reasonable request.
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