Multiple Classes of MSL Binding Sites Target Dosage Compensation to the X Chromosome of Drosophila

Oh, Hyangyee; Bone, James R.; Kuroda, Mitzi I.

doi:10.1016/j.cub.2004.03.004

Cited by 70 publications

(112 citation statements)

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“…Binding sites would, in this scenario, be determined by the concentration of many recognition elements in a particular DNA sequence. Our observations are compatible with the "affinities" model for targeting of the DCC (Demakova et al 2003;Fagegaltier and Baker 2004;Oh et al 2004b;Dahlsveen et al 2006). However, affinities alone fail to explain the recent observation that the MSL2 protein exhibits exceptionally stable binding to the male X chromosome, assayed by FRAP and FLIP (Straub et al 2005c), as sites of low affinity would be expected to demonstrate highly dynamic binding to the MSL complex.…”

Section: A Speculative Model Of DCC Targeting Based On a Two-step (Losupporting

confidence: 88%

“…Accordingly, the MSL proteins were proposed to recognize the X via the ∼35 high-affinity "entry sites," from where they could spread to bind the remaining target sites by an unknown mechanism (Lyman et al 1997;Kelley et al 1999). Recent studies of flies with altered DCC concentrations, X to autosome translocations, and analysis of new "entry sites" suggest that the entry sites are simply high-affinity sites in a continuum of affinity sites dispersed along the X chromosome (Demakova et al 2003;Fagegaltier and Baker 2004;Oh et al 2004b;Dahlsveen et al 2006). The most recent model therefore proposes that X-chromosome binding is governed largely or even solely by DNA elements of a degenerate nature (for review, see Straub et al 2005a).…”

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confidence: 99%

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Chromosome-wide gene-specific targeting of theDrosophiladosage compensation complex

Gilfillan¹,

Straub²,

Wit³

et al. 2006

Genes Dev.

148

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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Section: A Speculative Model Of DCC Targeting Based On a Two-step (Losupporting

confidence: 88%

mentioning

confidence: 99%

Chromosome-wide gene-specific targeting of theDrosophiladosage compensation complex

Gilfillan¹,

Straub²,

Wit³

et al. 2006

Genes Dev.

148

209

View full text Add to dashboard Cite

show abstract

“…As yet, not enough of these examples have been described to deduce common sequence characteristics that can be tested experimentally by mutagenesis. In stable translocation stocks, spreading of MSL complexes from the X into contiguous autosomal sequences is not evident (Fagegaltier and Baker 2004;Oh et al 2004). Therefore, even if spreading of MSL complexes is a major mechanism for covering the X chromosome, there is very likely an additional characteristic of the X that causes MSL complex to strongly favor X over autosomal binding.…”

Section: Transition From Initiation Sites To Target Genesmentioning

confidence: 99%

Dosage Compensation inDrosophila

Lucchesi

Kuroda

2015

Cold Spring Harb Perspect Biol

192

173

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SUMMARYDosage compensation in Drosophila increases the transcription of genes on the single X chromosome in males to equal that of both X chromosomes in females. Site-specific histone acetylation by the malespecific lethal (MSL) complex is thought to play a fundamental role in the increased transcriptional output of the male X. Nucleation and sequence-independent spreading of the complex to active genes serves as a model for understanding the targeting and function of epigenetic chromatin-modifying complexes. Interestingly, two noncoding RNAs are key for MSL assembly and spreading to active genes along the length of the X chromosome.

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“…However, translocations of the Drosophila X chromosome to autosomes attract the MSL complex but fail to direct spreading of these proteins into autosomal chromatin. (11) roX transcripts produced from an autosome may travel in trans to the X chromosome, and roX1 À roX2 À males are rescued by autosomal insertions of roX transgenes, further distinguishing the properties of the mammalian Xist and Drosophila roX RNAs. (10) Targeting to the fly X chromosome combines elements of Fig.…”

Section: Discussionmentioning

confidence: 99%

“…(11,13,14) This raises the question of whether the interesting genetic properties of C. elegans recognition element arrays originate solely from increasing the number of recognition elements in the nucleus, or if their organization into arrays contributes to their effectiveness.…”

Section: Discussionmentioning

confidence: 99%

Worm chromosomes call for recognition!

Rattner¹,

Meller²

2004

BioEssays

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SummaryMany organisms face a dilemma rooted in the unequal numbers of X chromosomes carried by the two sexes and the need to maintain equivalent expression of X-linked genes. Several strategies have arisen to cope with this problem. All rely on accurately targeting epigenetic modifications to entire chromosomes. Targeting results from the action of recognition elements that attract modification and may rely on spreading of modification in cis along the affected chromosome. A recent report describing the first X chromosome recognition element from C. elegans opens the way to defining the relative contributions of these factors to the compensation of Xlinked gene expression in worms. (1) Extrachromosomal arrays composed of a C. elegans recognition element attract proteins that modify the C. elegans X chromosomes and interact genetically with mutations disrupting compensation. Moreover, examination of X:A translocations provides the first evidence for spreading of modification along C. elegans X chromosomes. Dosage compensation: one problem with different solutions One of the primary distinctions between the sexes of many species is the number of sex chromosomes. The heterogametic sex (XY or X0) typically results in male development, and female or hermaphrodite development occurs in the sex carrying two copies of the same chromosome (XX). As most X-linked genes encode functions that are required equally in both sexes, inequality in the number of sex chromosomes poses a fundamental challenge: the need for a mechanism that ensures the production of similar amounts of X-linked gene products regardless of the number of X chromosomes present. At least three different solutions have independently evolved in mammals, flies and the worm C. elegans. These strategies, grouped under the term 'dosage compensation', appear different at a first glance but present remarkable similarities. In mammals, dosage compensation between XY males and XX females occurs by the transcriptional silencing of one randomly chosen X chromosome in each female cell. (2) In flies, XY males increase transcription from most X-linked genes. (3) Hermaphrodite worms (XX) continue to transcribe both X chromosomes, but at half the rate of the single male X. (4) These divergent strategies arrive at a similar outcome: both sexes express similar amounts of most X-linked gene products. Each mechanism is based on the recruitment of chromatin-modifying factors to the X chromosome. These factors achieve a stable, epigenetic modification of chromatin structure resulting in altered gene expression, the central feature of dosage compensation.Targeting the X chromosome A shared requirement of each system is the need to accurately target modification to an entire chromosome, or in C. elegans, a pair of X chromosomes. An element of danger is implicit in the mammalian strategy as silencing is directed to one chromosome, but the identical homologue must remain active. This dilemma is solved by designating a single X inactivation center (Xic) to direct X inactivation in ci...

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Multiple Classes of MSL Binding Sites Target Dosage Compensation to the X Chromosome of Drosophila

Cited by 70 publications

References 14 publications

Chromosome-wide gene-specific targeting of theDrosophiladosage compensation complex

Chromosome-wide gene-specific targeting of theDrosophiladosage compensation complex

Dosage Compensation inDrosophila

Worm chromosomes call for recognition!

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