Developmental regulation of bovine insulin-like growth factor-II (IGF-II) gene expression: homology between bovine transcripts and human IGF-II exons

Abstract

Initial observations have indicated similarities between bovine and human IGF-II production during development. The aim of the present study was to investigate whether cattle could provide an experimental model that would mimic the complex pattern of human IGF-II gene expression. Expression of bovine IGF-II gene during development was studied by RNA hybridization using various human IGF-II probes. In fetal tissues and in adult muscle, the bovine IGF-II gene was expressed as a family of eight transcripts ranging in size from 5.2 to 1.1 kb. In adult bovine liver, a major IGF-II transcript of 4.4 kb was expressed that could not be detected in any fetal or adult extra-hepatic tissue. During fetal life, quantitative IGF-II mRNA expression differed in liver and muscle, and the relative amounts of the different transcripts varied with the tissue of origin. These observations suggest that the regulation of bovine IGF-II gene expression is specific to the stage of development and the tissue concerned. Moreover its pattern is very similar to that in its human counterpart. In order to identify a putative homology between human and bovine gene structures, bovine mRNAs were examined for cross-hybridization with various non-coding exons of the human gene. Cross-hybridization was detected with human untranslated exons 5 and 6, suggesting the presence of two distinct promoters similar to the human promoters P3 and P4. The 4.4 kb mRNA species expressed in adult bovine liver failed to hybridize to a probe for human exons 1 and 2, suggesting that the leader sequences of this transcript were different from those present in the human gene. Finally, results obtained with a probe containing the 3' untranslated end of exon 9 suggested the presence of at least two polyadenylation sites in the bovine gene. Although differences in IGF-II gene structures were found between cattle and man, the similarities in the pattern of gene expression between the two species suggest that cattle may be a useful model to investigate some developmental aspects of the expression of the human IGF-II gene.

Atlas of tissue- and developmental stage specific gene expression for the bovine insulin-like growth factor (IGF) system

“…This is based on an IGF2 -P0 expression level in juvenile liver similar to that in fetal skeletal muscle and the fact that relative transcript abundance of IGF2 -P1e2 and IGF2 -P1e3 in juvenile liver was 130-fold and 15-fold higher than in fetal muscle. Our demonstration of increased activity of IGF2- P1 promoter in postnatal liver where IGF2- P2, IGF2- P3 and IGF2- P4 activity decreases, is consistent with the developmental shift in promoter activity reported for human [ 46 , 50 ], pig [ 44 ], sheep [ 42 , 91 ] and bovine [ 92 ].…”

“…Postnatal decline in expression of global IGF2 transcript was considerably stronger than for IGF1 , highlighting the special role of IGF2 in prenatal growth and development described previously [ 126 – 128 ]. Significant downregulation of IGF2 after birth has been reported for cattle, sheep and human [ 90 – 92 , 98 , 129 ]. In rat, IGF2 transcripts were undetectable by Northern blot in all adult tissues except brain, spinal cord and striated muscle [ 13 , 130 , 131 ].…”

Insulin-like growth factor II (IGF-II) mRNA expression during skeletal muscle development of double-muscled and normal bovine foetuses

“…In Semitendinosus muscle from normal and double-muscled bovine foetuses, the IGF-II gene is expressed as a family of transcripts, as is the case in other mammalian species [16,19,25,32] [4]. Strong homologies have been shown to exist between the coding regions of bovine and human genes [18].…”

“…Possible [31]. The bovine 5.1 kb transcript appears to be homologous to the human 6.0 kb transcript, and the bovine 4.0 kb to the human 4.8 kb transcript, respectively [4]. Thus, it may be engaged in protein synthesis of IGF-II.…”

Promoter-Specific Expression of the Imprinted IGF2 Gene in Cattle (Bos taurus)1

“…Although the bovine IGF2 has been shown to be preferentially paternally expressed in the placenta and liver of hybrid Bos gaurus and Bos taurus fetuses [10], has at least two polyadenylation sites, and has multiple transcripts of different sizes [22], a detailed analysis of the age-, tissue-, or promoter-specific allelic expression of the bovine IGF2 gene has not been reported. This is primarily due to a lack of sequence information for the bovine IGF2 gene.…”