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Transcriptomic prediction of pig Leg1s functions in HepG2 cells

ABSTRACT: The newly identified liver-enriched gene 1 (Leg1) encodes a protein with characteristic Domain of Unknown Function 781 (DUF781/LEG1) domain constituting a protein family with only one member. Functional study in zebrafish suggested that Leg1 genes were involved in the liver development, while the platypus MLP homolog that was enriched in mammary gland and milk acts as an anti-bacterial substance. However, no functional study on eutherian Leg1s has been published at present. Thus, we first report here a functional prediction research in a cellular model. As previously reported, eutherian Leg1s could be classified into three paralogous groups. Pig has all three Leg1 genes, while human and mouse only have retained Leg1a. Hence, pig is an ideal model to study the gene function. RNA-seq was then performed by overexpression of pig Leg1s and platypus MLP in the HepG2 cells. Enrichment analysis showed that pLeg1a and pLeg1b might be of little function in the liver cell; however, pLeg1c was probably involved in the ER stress response and protein folding. Additionally, gene set enrichment analysis revealed that platypus MLP has anti-bacterial activity confirming the functional study in the platypus. Therefore, our study, from the transcriptomic perspective of view, concluded that the mammalian Leg1s have different functions in the liver cells due to subfunctionalization of the paralogous genes.

ORGANISM(S): Homo sapiens

PROVIDER: GSE145329 | GEO | 2020/05/01

REPOSITORIES: GEO

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Evolutionary and Molecular Characterization of liver enriched gene 1

Project description:Liver enriched gene 1 (Leg1) is a newly identified gene with few functional information. To know the function of Leg1 in mammals, a phylogenetic study was first conducted and indicated that Leg1 is an ancient gene, existing from bacteria to mammals. Analysis of pig genome shows the presence of three copies of pig Leg1s (pLeg1), which could be grouped to Leg1a, Leg1b, and Leg1c clades, respectively. Purifying force acts upon the evolution of Leg1 genes, making them highly likely be functional constraint.Additionally, expression analysis of pLeg1 in combination with the available expression data of human and mouse Leg1s suggests that the eutherian Leg1s might preserve similar function in contrary to those of zebrafish and platypus. Therefore, pLeg1a might provide essential information regarding eutherian Leg1a. In our work, pLeg1a and its coding protein pLEG1a display high similarities to its human and mouse counterparts in terms of gene organization, expression pattern, glycosylation, structures. Moreover, preliminary functional study using RNA-seq suggested that pLeg1a involves in the lipid homeostasis. In conclusion, our study has provided some basic information regarding the evolution, and function of Leg1 genes, which could be applied to further validation of Leg1.

2020-03-23 | GSE134920 | GEO

Evolution of Gene Expression in the Uterine Cervix related to Steroid Signaling: Conserved features in the regulation of cervical remodeling.

Project description:The uterine cervix is the boundary structure between the uterus and the vagina and is a key component of the female reproductive tract for the maintenance of pregnancy and timing of parturition. Here we report on a comparative transcriptomic study of the cervix of four placental mammal species, mouse, guinea pig, rabbit and the basal eutherian mammal, armadillo, Dasypus novemcinctus, and one marsupial species, Monodelphis domestica. Our aim is to investigate the evolution of cervical gene expression as related to putative mechanisms for functional progesterone withdrawal. Our main findings are: 1) The patterns of gene expression found in eutherian species is consistent with the notion that an increase in the ratio of E/P4 signaling strength is critical for cervical remodeling. How the increased E/P4 ratio is achieved, however, is variable between eutherian species. 2) None of the genes related to steroid signaling modulated in eutherian species change expression during opossum gestation, suggesting that the role of P4 signaling in cervical remodeling evolved after the common ancestor of marsupials and placental mammals. 3) A tendency for decreased expression of progesterone receptor co-activators (NCOA1, -2 and -3, and CREBP) towards term is a shared derived feature of eutherians. This finding suggests that parturition is associated with broad scale histone de-acetylation. We tested this hypothesis by performing Western-blotting on mouse cervix and found evidence for a striking degree of histone de-acetylation in labor. This finding may have important implications for the control of premature cervical remodeling and preterm birth in humans.

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Hepatic irradiated pigs develop radiation induced veno-occlusive liver disease with ferroptosis

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Nuclear pore complex evolution: A trypanosome Mlp analog functions in chromosomal segregation but lacks transcriptional barrier activity

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2014-04-03 | E-GEOD-56436 | biostudies-arrayexpress

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2023-02-08 | GSE214245 | GEO

Conservation of small RNA pathways in platypus

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Project description:A major challenge in biology is to determine how evolutionarily novel characters originate, however, mechanistic explanations for the origin of novelties are almost completely unknown. The evolution of mammalian pregnancy is an excellent system in which to study the origin of novelties because extant mammals preserve major stages in the transition from egg-laying to live-birth. To determine the molecular bases of this transition, we characterized the pregnant/gravid uterine transcriptome from tetrapods, including species in the three major mammalian lineages, and used ancestral transcriptome reconstruction to trace the evolutionary history of uterine gene expression. We show that thousands of genes evolved or lost uterine expression during the origins of mammalian pregnancy, including the loss of genes responsible for the mineralization of the eggshell in the Mammalian and Therian stem-lineages, and the recruitment of genes into uterine expression that mediate maternal-fetal communication and maternal immunotolerance of the fetal allograft in the Therian and Eutherian stem-lineages. Our results indicate that one of the defining mammalian novelties evolved through a step-wise process that dramatically changed uterine gene expression, generating a suite of evolutionary innovations that support prolonged gestations. We report genome-wide gene expression generated by mRNA-Seq from the pregnant endometrium of dog, armadillo, and the platypus.

2015-01-30 | E-GEOD-57714 | biostudies-arrayexpress

Proteomic analysis of liver tissue from a pig model of mutant INS gene induced diabetes of youth (MIDY)

Project description:To evaluate functional consequences of insulin-deficient diabetes mellitus for the liver, we used a genetically engineered pig model of mutant INS gene induced diabetes of youth (MIDY). Liver samples of MIDY pigs and wild-type (WT) littermate controls were analyzed by label-free proteomics to reveal pathways and key drivers significantly affected by chronic insulin deficiency and hyperglycemia.

2019-11-12 | PXD011536 | Pride

Nuclear pore complex evolution: A trypanosome Mlp analog functions in chromosomal segregation but lacks transcriptional barrier activity

2014-04-03 | GSE56436 | GEO

The cardiac syndecan-4 interactome:A role for syndecan-4 innuclear translocation of muscle LIM protein (MLP)

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2019-04-09 | PXD011249 | Pride

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