The mouse Lsp1 and Tnnt3 genes are 4.3 kb apart on distal mouse Chromosome 7

Misener, Virginia L.; Wielowieyski, Andrzej; Brennan, Laurie A.; Beebakhee, Glen; Jongstra, Jan

doi:10.1007/s003359900880

Cited by 6 publications

(2 citation statements)

References 21 publications

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“…The gene encoding the fastermigrating isoform of skeletal muscle troponin-T (TNNT3) is located 55 kb from L23MRP (47). The linkage of Tnnt3 to H19 is conserved in mice (27). Tnnt3 is biallelically expressed and shows expression parallel to that of H19 in different adult skeletal muscle types, which led to the suggestion that H19 and TNNT3 have common enhancer elements (47).…”

Section: Nctc1 Is Not Essential For Normal Mouse Developmentmentioning

confidence: 99%

Regulatory Mechanisms at the MouseIgf2/H19 Locus

Kaffer

Grinberg

Pfeifer

2001

Molecular and Cellular Biology

100

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The closely linked H19 and Igf2 genes show highly similar patterns of gene expression but are reciprocally imprinted. H19 is expressed almost exclusively from the maternally inherited chromosome, while Igf2 expression is mostly from the paternal chromosome. In humans, loss of imprinting at this locus is associated with tumors and with developmental disorders. Monoallelic expression at the imprinted Igf2/H19 locus occurs by at least two distinct mechanisms: a developmentally regulated silencing of the paternal H19 promoter, and transcriptional insulation of the maternal Igf2 promoters. Both mechanisms of allele-specific silencing are ultimately dependent on a common cis-acting element located just upstream of the H19 promoter. The coordinated expression patterns and some experimental data support the idea that positive regulatory elements are also shared by the two genes. To clarify the organization and function of positive and negative regulatory elements at the H19/Igf2 locus, we analyzed two mouse mutations. First, we generated a deletion allele to localize enhancers used in vivo for expression of both H19 and Igf2 in mesodermal tissues to sequences downstream of the H19 gene. Coincidentally, we demonstrated that some expression of Igf2 is independent of the shared enhancer element. Second, we used this new information to further characterize an ectopic H19 differentially regulated region and the associated insulator. We demonstrated that its activity is parent-oforigin dependent. In contrast to recent results from Drosophila model systems; we showed that this duplication of a mammalian insulator does not interfere with its normal function. Implications of these findings for current models for monoallelic gene expression at this locus are discussed.Igf2 and H19 are closely linked and reciprocally imprinted genes located on the distal end of mouse chromosome 7 (48) (Fig. 1a). The regulation of the two genes has been intensively studied both as a model system for understanding mechanisms of genomic imprinting and because dysregulation of IGF2 in humans is associated with the developmental disorder Beckwith-Wiedemann syndrome and with many types of tumors (33). The two genes are part of a large cluster of imprinted genes whose organization and monoallelic expression patterns are well conserved between mice and humans (30, 31). H19 represents one limit of this imprinted cluster, as the next known genes, Nctc1 and L23mrp, are both biallelically expressed (19, 49).Both H19 and Igf2 are highly expressed during fetal and early postnatal development and show essentially identical spatial and temporal specificities. In fact, as suggested by their close linkage, their reciprocal imprinting, and their overlapping expression patterns, the two genes share transcriptional regulatory elements. The paternal silencing of H19 and maternal repression of Igf2 both depend on a common cis-acting element, here called the H19ICE (for H19 imprinting control element), located upstream of the H19 promoter (Fig. 1a) (20,42). The boundarie...

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Section: Nctc1 Is Not Essential For Normal Mouse Developmentmentioning

confidence: 99%

Regulatory Mechanisms at the MouseIgf2/H19 Locus

Kaffer

Grinberg

Pfeifer

2001

Molecular and Cellular Biology

100

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“…Mouse Lsp1 codes for a lymphocyte-specific calcium-binding protein with unknown function (Jongstra et al 1988) and was previously mapped upstream of Tnnt3 (Misener et al 1998). The chicken gene consisted of 11 exons as the mammalian ortholog.…”

Section: Identification and Characterization Of Chicken Cd81/tapa1 Pmentioning

confidence: 99%

Structural and functional analysis of a 0.5-Mb chicken region orthologous to the imprinted mammalianAscl2/Mash2–Igf2–H19region

Yokomine¹,

Shirohzu²,

Purbowasito³

et al. 2004

Genome Res.

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Previous studies revealed that Igf2 and Mpr/Igf2r are imprinted in eutherian mammals and marsupials but not in monotremes or birds. Igf2 lies in a large imprinted cluster in eutherians, and its imprinting is regulated by long-range mechanisms. As a step to understand how the imprinted cluster evolved, we have determined a 490-kb chicken sequence containing the orthologs of mammalian Ascl2/Mash2, Ins2 and Igf2. We found that most of the genes in this region are conserved between chickens and mammals, maintaining the same transcriptional polarities and exon-intron structures. However, H19, an imprinted noncoding transcript, was absent from the chicken sequence. Chicken ASCL2/CASH4 and INS, the orthologs of the imprinted mammalian genes, showed biallelic expression, further supporting the notion that imprinting evolved after the divergence of mammals and birds. The H19 imprinting center and many of the local regulatory elements identified in mammals were not found in chickens. Also, a large segment of tandem repeats and retroelements identified between the two imprinted subdomains in mice was not found in chickens. Our findings show that the imprinted genes were clustered before the emergence of imprinting and that the elements associated with imprinting probably evolved after the divergence of mammals and birds.

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Characterization of a 500-kb Contig Spanning the Region between c-Ha-Ras and MUC2 on Chromosome 11p15.5

Paris

Williams

2000

Genomics

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The mouse Lsp1 and Tnnt3 genes are 4.3 kb apart on distal mouse Chromosome 7

Cited by 6 publications

References 21 publications

Regulatory Mechanisms at the MouseIgf2/H19 Locus

Regulatory Mechanisms at the MouseIgf2/H19 Locus

Structural and functional analysis of a 0.5-Mb chicken region orthologous to the imprinted mammalianAscl2/Mash2–Igf2–H19region

Characterization of a 500-kb Contig Spanning the Region between c-Ha-Ras and MUC2 on Chromosome 11p15.5

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