A global genomic transcriptional code associated with CNS-expressed genes

Bailey, Peter J.; Klos, Joanna M.; Andersson, Elisabet; Karlén, Mattias; Källström, Magdalena; Ponjavic, Jasmina; Muhr, Jonas; Lenhard, Boris; Sandelin, Albin; Ericson, Johan

doi:10.1016/j.yexcr.2006.06.017

Cited by 41 publications

(46 citation statements)

References 62 publications

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“…We required HCNEs to be conserved at 98% identity over at least 50 bp in all four pairwise comparisons. To focus on elements that are most likely to function in regulation of transcription, we discarded elements that partially or entirely overlapped exons (Bejerano et al 2004;Glazov et al 2005;Woolfe et al 2005;Bailey et al 2006). There were 6779 HCNEs, with a median size of 59 bp and a maximum of 157 bp.…”

Section: Resultsmentioning

confidence: 99%

“…Many HCNEs have been characterized as long-range enhancers, first in studies of individual genes (Gottgens et al 2000;Sumiyama and Ruddle 2003;Kimura-Yoshida et al 2004;Milewski et al 2004), followed by systematic studies in zebrafish, Xenopus, and mouse (de la Calle-Mustienes et al 2005;Shin et al 2005;Woolfe et al 2005;Pennacchio et al 2006). Genome-wide analyses of HCNE sequences have detected several overrepresented motifs that are believed to be associated with context-specific enhancer activity (Bailey et al 2006;Pennacchio et al 2007). …”

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confidence: 99%

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Genomic regulatory blocks underlie extensive microsynteny conservation in insects

Engström¹,

Sui²,

Drivenes³

et al. 2007

Genome Res.

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192

208

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Insect genomes contain larger blocks of conserved gene order (microsynteny) than would be expected under a random breakage model of chromosome evolution. We present evidence that microsynteny has been retained to keep large arrays of highly conserved noncoding elements (HCNEs) intact. These arrays span key developmental regulatory genes, forming genomic regulatory blocks (GRBs). We recently described GRBs in vertebrates, where most HCNEs function as enhancers and HCNE arrays specify complex expression programs of their target genes. Here we present a comparison of five Drosophila genomes showing that HCNE density peaks centrally in large synteny blocks containing multiple genes. Besides developmental regulators that are likely targets of HCNE enhancers, HCNE arrays often span unrelated neighboring genes. We describe differences in core promoters between the target genes and the unrelated genes that offer an explanation for the differences in their responsiveness to enhancers. We show examples of a striking correspondence between boundaries of synteny blocks, HCNE arrays, and Polycomb binding regions, confirming that the synteny blocks correspond to regulatory domains. Although few noncoding elements are highly conserved between Drosophila and the malaria mosquito Anopheles gambiae, we find that A. gambiae regions orthologous to Drosophila GRBs contain an equivalent distribution of noncoding elements highly conserved in the yellow fever mosquito Aëdes aegypti and coincide with regions of ancient microsynteny between Drosophila and mosquitoes. The structural and functional equivalence between insect and vertebrate GRBs marks them as an ancient feature of metazoan genomes and as a key to future studies of development and gene regulation.

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Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

Genomic regulatory blocks underlie extensive microsynteny conservation in insects

Engström¹,

Sui²,

Drivenes³

et al. 2007

Genome Res.

Self Cite

192

208

View full text Add to dashboard Cite

show abstract

“…Because experimental studies of CNEs in these regions have frequently uncovered cis-regulatory functions affecting the nearby developmental genes 16,[82][83][84][85] , the substantial innovations in these regions are candidates for genetic changes underlying differential morphological and neurological evolution in mammalian lineages. This pattern would be consistent with the notion that modification of regulatory networks has been a major force in the evolution of animal diversity [86][87][88] .…”

Section: Conserved Sequence Elementsmentioning

confidence: 99%

Genome of the marsupial Monodelphis domestica reveals innovation in non-coding sequences

Mikkelsen¹,

Wakefield²,

Aken³

et al. 2007

Nature

664

592

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We report a high-quality draft of the genome sequence of the grey, short-tailed opossum (Monodelphis domestica). As the first metatherian ('marsupial') species to be sequenced, the opossum provides a unique perspective on the organization and evolution of mammalian genomes. Distinctive features of the opossum chromosomes provide support for recent theories about genome evolution and function, including a strong influence of biased gene conversion on nucleotide sequence composition, and a relationship between chromosomal characteristics and X chromosome inactivation. Comparison of opossum and eutherian genomes also reveals a sharp difference in evolutionary innovation between protein-coding and non-coding functional elements. True innovation in protein-coding genes seems to be relatively rare, with lineage-specific differences being largely due to diversification and rapid turnover in gene families involved in environmental interactions. In contrast, about 20% of eutherian conserved non-coding elements (CNEs) are recent inventions that postdate the divergence of Eutheria and Metatheria. A substantial proportion of these eutherian-specific CNEs arose from sequence inserted by transposable elements, pointing to transposons as a major creative force in the evolution of mammalian gene regulation.

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“…Taken together with previous studies, these results suggest that the spi signaling pathway may play at least two roles in promoting survival of midline glia: (1) activating wrapper, needed for neuron-glial interactions and (2) phosphorylating, thereby inactivating head involution defective (Bergmann et al 2002), which would otherwise cause programmed cell death in midline glia. Sox, POU, and homeodomain proteins in CNS transcriptional regulation: Many genes expressed in the CNS of metazoan organisms are regulated through synergistic interactions between Sox HMG-containing proteins and POU domain proteins (Ambrosetti et al 2000;Ma et al 2000;Tanaka et al 2004;Bailey et al 2006). Recently, many vertebrate genes expressed in the developing CNS have been shown to contain highly conserved noncoding DNA regions enriched for binding sites for three classes of transcription factors: Sox, POU, and homeodomain proteins (Bailey et al 2006).…”

Section: Discussionmentioning

confidence: 99%

“…Sox, POU, and homeodomain proteins in CNS transcriptional regulation: Many genes expressed in the CNS of metazoan organisms are regulated through synergistic interactions between Sox HMG-containing proteins and POU domain proteins (Ambrosetti et al 2000;Ma et al 2000;Tanaka et al 2004;Bailey et al 2006). Recently, many vertebrate genes expressed in the developing CNS have been shown to contain highly conserved noncoding DNA regions enriched for binding sites for three classes of transcription factors: Sox, POU, and homeodomain proteins (Bailey et al 2006). Experiments indicated that Sox and POU proteins work together to activate, while homeodomain proteins repress and limit expression of CNS genes.…”

Section: Discussionmentioning

confidence: 99%

Identification of Motifs That Are Conserved in 12 Drosophila Species and Regulate Midline Glia vs. Neuron Expression

2008

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Functional complexity of the central nervous system (CNS) is reflected by the large number and diversity of genes expressed in its many different cell types. Understanding the control of gene expression within cells of the CNS will help reveal how various neurons and glia develop and function. Midline cells of Drosophila differentiate into glial cells and several types of neurons and also serve as a signaling center for surrounding tissues. Here, we examine regulation of the midline gene, wrapper, required for both neuron-glia interactions and viability of midline glia. We identify a region upstream of wrapper required for midline expression that is highly conserved (87%) between 12 Drosophila species. Site-directed mutagenesis identifies four motifs necessary for midline glial expression: (1) a Single-minded/Tango binding site, (2) a motif resembling a pointed binding site, (3) a motif resembling a Sox binding site, and (4) a novel motif. An additional highly conserved 27 bp are required to restrict expression to midline glia and exclude it from midline neurons. These results suggest short, highly conserved genomic sequences flanking Drosophila midline genes are indicative of functional regulatory regions and that small changes within these sequences can alter the expression pattern of a gene.

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A global genomic transcriptional code associated with CNS-expressed genes

Cited by 41 publications

References 62 publications

Genomic regulatory blocks underlie extensive microsynteny conservation in insects

Genomic regulatory blocks underlie extensive microsynteny conservation in insects

Genome of the marsupial Monodelphis domestica reveals innovation in non-coding sequences

Identification of Motifs That Are Conserved in 12 Drosophila Species and Regulate Midline Glia vs. Neuron Expression

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