Regulation of the stem cell leukemia (
            <i>SCL</i>
            ) gene: A tale of two fishes

Barton, Linda; Göttgens, Berthold; Gering, Martin; Gilbert, James; Grafham, Darren; Rogers, Jane; Bentley, David; Patient, Roger; Green, Anthony

doi:10.1073/pnas.101532998

Cited by 47 publications

(38 citation statements)

References 64 publications

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“…Comparative genomic sequence analysis offers a powerful strategy for the identification of functionally relevant gene regulatory elements that may be later subjected to experimental evaluation. Conservation of regulatory sequences in noncoding regions between pufferfish and mammalian orthologs has been found in a number of genes, with some elements also displaying equivalent function Popperl et al 1995;Barton et al 2001). On the other hand, such comparative analyses between human and mouse genomic portions frequently result in the detection of many regions of similarity (Hardison et al 1997;Dubchak et al 2000;Gottgens et al 2000;Loots et al 2000) for which functional relevance is difficult to establish.…”

Section: Comparative Analysis Of Dystrophin Vertebrate Locimentioning

confidence: 99%

Comparative Analysis of Vertebrate Dystrophin Loci Indicate Intron Gigantism as a Common Feature

Pozzoli

Elgar²,

Cagliani

et al. 2003

Genome Res.

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The human DMD gene is the largest known to date, spanning > 2000 kb on the X chromosome. The gene size is mainly accounted for by huge intronic regions. We sequenced 190 kb of Fugu rubripes (pufferfish) genomic DNA corresponding to the complete dystrophin gene (FrDMD) and provide the first report of gene structure and sequence comparison among dystrophin genomic sequences from different vertebrate organisms. Almost all intron positions and phases are conserved between FrDMD and its mammalian counterparts, and the predicted protein product of the Fugu gene displays 55% identity and 71% similarity to human dystrophin. In analogy to the human gene, FrDMD presents several-fold longer than average intronic regions. Analysis of intron sequences of the human and murine genes revealed that they are extremely conserved in size and that a similar fraction of total intron length is represented by repetitive elements; moreover, our data indicate that intron expansion through repeat accumulation in the two orthologs is the result of independent insertional events. The hypothesis that intron length might be functionally relevant to the DMD gene regulation is proposed and substantiated by the finding that dystrophin intron gigantism is common to the three vertebrate genes.

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Section: Comparative Analysis Of Dystrophin Vertebrate Locimentioning

confidence: 99%

Comparative Analysis of Vertebrate Dystrophin Loci Indicate Intron Gigantism as a Common Feature

Pozzoli

Elgar²,

Cagliani

et al. 2003

Genome Res.

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“…A comprehensive analysis of the transcriptional regulation of Scl has identified several tissuespecific enhancers that are required for its appropriate expression (Barton et al, 2001;Gottgens et al, 2002;Sinclair et al, 1999). Interestingly, the enhancer specific for hematopoietic progenitors has GATA sites that are crucial for Scl enhancer activity in vivo.…”

Section: An E Box-binding Factor Is Required For Gata2 Endothelial Enmentioning

confidence: 99%

AGata2intronic enhancer confers its pan-endothelia-specific regulation

et al. 2007

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GATA-2, a transcription factor that has been shown to play important roles in multiple organ systems during embryogenesis, has been ascribed the property of regulating the expression of numerous endothelium-specific genes. However,the transcriptional regulatory hierarchy governing Gata2 activation in endothelial cells has not been fully explored. Here, we document GATA-2 endothelial expression during embryogenesis by following GFP expression in Gata2-GFP knock-in embryos. Using founder transgenic analyses, we identified a Gata2 endothelium enhancer in the fourth intron and found that Gata2 regulation by this enhancer is restricted to the endocardial, lymphatic and vascular endothelium. Whereas disruption of three ETS-binding motifs within the enhancer diminished its activity, the ablation of its single E box extinguished endothelial enhancer-directed expression in transgenic mice. Development of the endothelium is known to require SCL(TAL1), and an SCL-E12 (SCL-Tcfe2a) heterodimer can bind the crucial E box in the enhancer in vitro. Thus, GATA-2 is expressed early in lymphatic, cardiac and blood vascular endothelial cells, and the pan-endothelium-specific expression of Gata2 is controlled by a discrete intronic enhancer.

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“…CNEs, and other similar highly conserved noncoding sequences, are found to cluster in the vicinity of genes implicated in transcriptional regulation and early development (Bejerano et al 2004a;Sandelin et al 2004;Woolfe et al 2005) and the majority of those tested in vivo (5/7 in mice, Nobrega et al 2003; 23/25 in fish, Woolfe et al 2005) drive expression of reporter genes in a temporal and spatial specific manner during early development. Many other studies around specific developmental genes have also identified highly conserved noncoding sequences between humans and fish that have enhancer activity (Zerucha et al 2000;Barton et al 2001;Lien et al 2002;Blader et al 2003; Lettice et al 2003;Dickmeis et al 2004;Kimura-Yoshida et al 2004;de la Calle-Mustienes et al 2005;Goode et al 2005). The association of these highly conserved sequences to genes implicated in the regulation in early development is most likely a result of the fundamental nature of the developmental process in vertebrates.…”

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confidence: 99%

Ancient duplicated conserved noncoding elements in vertebrates: A genomic and functional analysis

McEwen¹,

Woolfe²,

Goode³

et al. 2006

Genome Res.

100

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Fish-mammal genomic comparisons have proved powerful in identifying conserved noncoding elements likely to be cis-regulatory in nature, and the majority of those tested in vivo have been shown to act as tissue-specific enhancers associated with genes involved in transcriptional regulation of development. Although most of these elements share little sequence identity to each other, a small number are remarkably similar and appear to be the product of duplication events. Here, we searched for duplicated conserved noncoding elements in the human genome, using comparisons with Fugu to select putative cis-regulatory sequences. We identified 124 families of duplicated elements, each containing between two and five members, that are highly conserved within and between vertebrate genomes. In 74% of cases, we were able to assign a specific set of paralogous genes with annotation relating to transcriptional regulation and/or development to each family, thus removing much of the ambiguity in identifying associated genes. We find that duplicate elements have the potential to up-regulate reporter gene expression in a tissue-specific manner and that expression domains often overlap, but are not necessarily identical, between family members. Over two thirds of the families are conserved in duplicate in fish and appear to predate the large-scale duplication events thought to have occurred at the origin of vertebrates. We propose a model whereby gene duplication and the evolution of cis-regulatory elements can be considered in the context of increased morphological diversity and the emergence of the modern vertebrate body plan.

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Regulation of the stem cell leukemia ( SCL ) gene: A tale of two fishes

Cited by 47 publications

References 64 publications

Comparative Analysis of Vertebrate Dystrophin Loci Indicate Intron Gigantism as a Common Feature

Comparative Analysis of Vertebrate Dystrophin Loci Indicate Intron Gigantism as a Common Feature

AGata2intronic enhancer confers its pan-endothelia-specific regulation

Ancient duplicated conserved noncoding elements in vertebrates: A genomic and functional analysis

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