Targeting Dosage Compensation to the X Chromosome of Drosophila Males

Oh, Hyun Jung; Bai, Xiaoying; Park, Y.; Bone, James R.; Kuroda, Mitzi I.

doi:10.1101/sqb.2004.69.81

Cited by 9 publications

(10 citation statements)

References 44 publications

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“…We hypothesize that the elements that define these pairs (and other such elements that may have escaped our attention) correspond to building blocks of DCC binding sites. Accordingly, a DCC binding site of given affinity for the complex would not be determined by a unique DNA sequence, but by clustering of variable combinations of short, degenerate sequence motifs, as previously suggested [8]. Individual low-affinity binding sites may not be unique to the X, but their clustering on the X may contribute to high-affinity binding [52].…”

Section: Discussionmentioning

confidence: 96%

“…Three high-affinity fragments (DBF12, DBF9, and DBF6) reside entirely within genes. It is possible that specific recruitment sites, such as those inferred to reside within our DBFs, have been enriched in and around genes that require dosage compensation during evolution [8], and consequently, high-affinity sites may represent loci that are particularly dosage sensitive. Previous experiments indicated that the DCC tends to bind to the coding regions of genes [49], and it was suggested that this was linked to transcriptional activity [50].…”

Section: Discussionmentioning

confidence: 99%

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Targeting Determinants of Dosage Compensation in Drosophila

et al. 2006

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The dosage compensation complex (DCC) in Drosophila melanogaster is responsible for up-regulating transcription from the single male X chromosome to equal the transcription from the two X chromosomes in females. Visualization of the DCC, a large ribonucleoprotein complex, on male larval polytene chromosomes reveals that the complex binds selectively to many interbands on the X chromosome. The targeting of the DCC is thought to be in part determined by DNA sequences that are enriched on the X. So far, lack of knowledge about DCC binding sites has prevented the identification of sequence determinants. Only three binding sites have been identified to date, but analysis of their DNA sequence did not allow the prediction of further binding sites. We have used chromatin immunoprecipitation to identify a number of new DCC binding fragments and characterized them in vivo by visualizing DCC binding to autosomal insertions of these fragments, and we have demonstrated that they possess a wide range of potential to recruit the DCC. By varying the in vivo concentration of the DCC, we provide evidence that this range of recruitment potential is due to differences in affinity of the complex to these sites. We were also able to establish that DCC binding to ectopic high-affinity sites can allow nearby low-affinity sites to recruit the complex. Using the sequences of the newly identified and previously characterized binding fragments, we have uncovered a number of short sequence motifs, which in combination may contribute to DCC recruitment. Our findings suggest that the DCC is recruited to the X via a number of binding sites of decreasing affinities, and that the presence of high- and moderate-affinity sites on the X may ensure that lower-affinity sites are occupied in a context-dependent manner. Our bioinformatics analysis suggests that DCC binding sites may be composed of variable combinations of degenerate motifs.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Targeting Determinants of Dosage Compensation in Drosophila

et al. 2006

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“…Furthermore, in each case there is evidence for spreading of the DCC process long distances along the chromosome from the sites of synthesis of those ncRNAs. However, the major differences between the mammalian and Drosophila systems is that in mammals, the DCC is involved in the inactivation of one of the X chromosomes, whereas in Drosophila, it results in the hyperactivation of the single X. Drosophila and mammals also differ in that Xist is limited to its action in cis, while roX RNAs and the MSL complex can also clearly act in trans (Oh et al 2004;Heard and Disteche 2006).…”

Section: X-chromosome Hyperactivation In Drosophilamentioning

confidence: 99%

“…High-affinity cis elements, such as within the roX genes, would not require additional cis-elements for recruiting MSL complexes, and this interaction is strengthened by roX RNA. Intermediate and weak-affinity cis-elements might require several cis-elements for robust binding, resulting in the ability to attract partial MSL complexes (Oh et al 2004).…”

Section: X-chromosome Hyperactivation In Drosophilamentioning

confidence: 99%

Eukaryotic regulatory RNAs: an answer to the ‘genome complexity’ conundrum

Prasanth¹,

Spector²

2007

Genes Dev.

364

305

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A large portion of the eukaryotic genome is transcribed as noncoding RNAs (ncRNAs). While once thought of primarily as "junk," recent studies indicate that a large number of these RNAs play central roles in regulating gene expression at multiple levels. The increasing diversity of ncRNAs identified in the eukaryotic genome suggests a critical nexus between the regulatory potential of ncRNAs and the complexity of genome organization. We provide an overview of recent advances in the identification and function of eukaryotic ncRNAs and the roles played by these RNAs in chromatin organization, gene expression, and disease etiology.

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“…The mechanism by which the DCC recognizes a single chromosome in the nucleus remains an enigma (Oh et al 2004a). Historically, three models of the mechanism for MSL targeting to the X have been proposed.…”

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confidence: 99%

Chromosome-wide gene-specific targeting of theDrosophiladosage compensation complex

Gilfillan¹,

Straub²,

Wit³

et al. 2006

Genes Dev.

147

209

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The dosage compensation complex (DCC) of Drosophila melanogaster is capable of distinguishing the single male X from the other chromosomes in the nucleus. It selectively interacts in a discontinuous pattern with much of the X chromosome. How the DCC identifies and binds the X, including binding to the many genes that require dosage compensation, is currently unknown. To identify bound genes and attempt to isolate the targeting cues, we visualized male-specific lethal 1 (MSL1) protein binding along the X chromosome by combining chromatin immunoprecipitation with high-resolution microarrays. More than 700 binding regions for the DCC were observed, encompassing more than half the genes found on the X chromosome. In addition, several rare autosomal binding sites were identified. Essential genes are preferred targets, and genes binding high levels of DCC appear to experience the most compensation (i.e., greatest increase in expression). DCC binding clearly favors genes over intergenic regions, and binds most strongly to the 3 end of transcription units. Within the targeted genes, the DCC exhibits a strong preference for exons and coding sequences. Our results demonstrate gene-specific binding of the DCC, and identify several sequence elements that may partly direct its targeting.[Keywords: Transcription; histone modification; chromatin remodeling; MSL complex; microarray; gene expression] Supplemental material is available at http://www.genesdev.org.

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Targeting Dosage Compensation to the X Chromosome of Drosophila Males

Cited by 9 publications

References 44 publications

Targeting Determinants of Dosage Compensation in Drosophila

Targeting Determinants of Dosage Compensation in Drosophila

Eukaryotic regulatory RNAs: an answer to the ‘genome complexity’ conundrum

Chromosome-wide gene-specific targeting of theDrosophiladosage compensation complex

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