Promoter-specific IGF2 imprinting status and its plasticity during human liver development

Development ◽  
1995 ◽  
Vol 121 (2) ◽  
pp. 309-316 ◽  
Author(s):  
T.J. Ekstrom ◽  
H. Cui ◽  
X. Li ◽  
R. Ohlsson

IGF2 has been shown to be expressed preferentially from the paternally derived allele, although the maternal allele can be found active during both prenatal and postnatal development as well as in neoplastic tumours in humans. We addressed here whether or not the biallelic expression patterns that can be seen during postnatal human liver development reflected a coordinated change in the activities of the four promoters of human IGF2. We show here that the P2, P3 and P4 promoters, but not the P1 promoter, display monoallelic activity in embryonic, neonatal and younger infant liver specimens. The P2, P3 and P4 promoters can, however, be found active either monoallelically or biallelically or even monoallelically on opposite parental alleles in older infant and adult liver specimens. In contrast, H19, which is closely linked to IGF2, is monoallelically expressed in all postnatal liver samples analysed. We conclude that the functional imprinting status of IGF2 during postnatal liver development appears to be promoter/enhancer-specific and either partly or completely independent of H19.

2006 ◽  
Vol 290 (1) ◽  
pp. G145-G155 ◽  
Author(s):  
Jennifer A. Sanders ◽  
Philip A. Gruppuso

The processes of liver development and regeneration involve regulation of a key network of transcription factors, the c -myc/ max/ mad network. This network regulates the expression of genes involved in hepatocyte proliferation, growth, metabolism, and differentiation. In previous studies on the expression and localization of c-Myc in the fetal and adult liver, we made the unexpected observation that c-Myc content was similar in the two. However, c-Myc was localized predominantly to the nucleolus in the adult liver. On the basis of this finding, we went on to characterize the expression patterns of the other members of the network, max and mad, comparing their regulation during late fetal development with the proliferation of mature hepatocytes that is seen in liver regeneration. We found that Max content, rather than being constitutive, as predicted by other studies, was elevated in the fetal liver compared with the adult liver. Its content correlated with hepatocyte proliferation during the perinatal transition. In contrast, mad4 expression was decreased in the fetal liver compared with the adult liver. Nucleolar localization of c-Myc coincided with changes in Max content. To explore this relationship, we overexpressed Max in cultured adult hepatocytes. High levels of Max resulted in a shift in c-Myc localization from nucleolar to diffuse nuclear. In contrast, liver regeneration was associated with an increase in c-Myc content but no change in Max content. We conclude that the regulation of Max content during liver development and its potential role in determining c-Myc localization are means by which Max may control the biological activity of the c-Myc/Max/Mad network during liver development.


Endocrinology ◽  
2013 ◽  
Vol 154 (3) ◽  
pp. 1321-1336 ◽  
Author(s):  
Francisco Gaytan ◽  
Susana Sangiao-Alvarellos ◽  
María Manfredi-Lozano ◽  
David García-Galiano ◽  
Francisco Ruiz-Pino ◽  
...  

Abstract Lin28 (also termed Lin28a) and Lin28b are related RNA-binding proteins, involved in the control of microRNA synthesis, especially of the let-7 family, with putative functions in early (embryo) development. However, their roles during postnatal maturation remain ill defined. Despite the general assumption that Lin28 and Lin28b share similar targets and functions, conclusive demonstration of such redundancy is still missing. In addition, recent observations suggest a role of Lin28 proteins in mammalian reproduction, which is yet to be defined. We document herein the patterns of RNA expression and protein distribution of Lin28 and Lin28b in mouse testis during postnatal development and in a model of hypogonadotropic hypogonadism as a result of inactivation of the kisspeptin receptor, Gpr54. Lin28 and Lin28b mRNAs were expressed in mouse testis across postnatal maturation, but their levels disparately varied between neonatal and pubertal periods, with peak Lin28 levels in infantile testes and sustained elevation of Lin28b mRNA in young adult male gonads, where relative levels of let-7a and let-7b miRNAs were significantly suppressed. In addition, Lin28 peptides displayed totally different patterns of cellular distribution in mouse testis: Lin28 was located in undifferentiated and type-A1 spermatogonia, whereas Lin28b was confined to spermatids and interstitial Leydig cells. These profiles were perturbed in Gpr54 null mouse testis, which showed preserved but irregular Lin28 signal and absence of Lin28b peptide, which was rescued by administration of gonadotropins, mainly hCG (as super-agonist of LH). In addition, increased relative levels of Lin28, but not Lin28b, mRNA and of let-7a/let-7b miRNAs were observed in Gpr54 KO mouse testes. Altogether, our data are the first to document the divergent patterns of cellular distribution and mRNA expression of Lin28 and Lin28b in the mouse testis along postnatal maturation and their alteration in a model of congenital hypogonadotropic hypogonadism. Our findings suggest distinct functional roles of these two related, but not overlapping, miRNA-binding proteins in the male gonad.


1999 ◽  
Vol 112 (4) ◽  
pp. 277-282 ◽  
Author(s):  
F. Quondamatteo ◽  
T. Knittel ◽  
M. Mehde ◽  
G. Ramadori ◽  
R. Herken

2021 ◽  
Vol 12 ◽  
Author(s):  
Biao Li ◽  
Jinzeng Yang ◽  
Yan Gong ◽  
Yu Xiao ◽  
Qinghua Zeng ◽  
...  

Liver is an important metabolic organ of mammals. During each transitional period of life, liver metabolism is programmed by a complex molecular regulatory system for multiple physiological functions, many pathways of which are regulated by hormones and cytokines, nuclear receptors, and transcription factors. To gain a comprehensive and unbiased molecular understanding of liver growth and development in Ningxiang pigs, we analyzed the mRNA, microRNA (miRNA), and proteomes of the livers of Ningxiang pigs during lactation, nursery, and fattening periods. A total of 22,411 genes (19,653 known mRNAs and 2758 novel mRNAs), 1122 miRNAs (384 known miRNAs and 738 novel miRNAs), and 1123 unique proteins with medium and high abundance were identified by high-throughput sequencing and mass spectrometry. We show that the differences in transcriptional, post-transcriptional, or protein levels were readily identified by comparing different time periods, providing evidence that functional changes that may occur during liver development are widespread. In addition, we found many overlapping differentially expressed genes (DEGs)/differentially expressed miRNAs (DEMs)/differentially expressed proteins (DEPs) related to glycolipid metabolism in any group comparison. These overlapping DEGs/DEMs/DGPs may play an important role in functional transformation during liver development. Short Time-series Expression Miner (STEM) analysis revealed multiple expression patterns of mRNA, miRNA, and protein in the liver. Furthermore, several diverse key Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, including immune defense, glycolipid metabolism, protein transport and uptake, and cell proliferation and development, were identified by combined analysis of DEGs and DGPs. A number of predicted miRNA–mRNA–protein pairs were found and validated by qRT-PCR and parallel reaction monitoring (PRM) assays. The results provide new and important information about the genetic breeding of Ningxiang pigs, which represents a foundation for further understanding the molecular regulatory mechanisms of dynamic development of liver tissue, functional transformation, and lipid metabolism.


2001 ◽  
Vol 353 (3) ◽  
pp. 673 ◽  
Author(s):  
Steven HUYGHE ◽  
Minne CASTEELS ◽  
Anneleen JANSSEN ◽  
Liesbeth MEULDERS ◽  
Guy P. MANNAERTS ◽  
...  

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