Gene Dosage Compensation in Drosophila Melanogaster

Lucchesi, John C.; Manning, Jerry E.

doi:10.1016/s0065-2660(08)60013-9

Cited by 125 publications

(65 citation statements)

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“…Among the four genes introduced above, two were newly discovered (male-specific lethal 1, msl1; and male-specific lethal 2, msl2), whereas the other two (maleless, mle; and male-specific lethal 3, msl3) had been previously identified by other investigators in natural populations (specific references to this early phase of the study of dosage compensation can be found in Lucchesi and Manning 1987). For ease of reference, all of the gene products identified to date, on the basis of the male-specific lethal phenotype of their loss-of-function mutations, are called the MSLs.…”

Section: The Phenomenon Of Dosage Compensation Was Discovered In Drosmentioning

confidence: 99%

Dosage Compensation inDrosophila

Lucchesi

Kuroda

2015

Cold Spring Harb Perspect Biol

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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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Section: The Phenomenon Of Dosage Compensation Was Discovered In Drosmentioning

confidence: 99%

Dosage Compensation inDrosophila

Lucchesi

Kuroda

2015

Cold Spring Harb Perspect Biol

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192

173

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“…Males dosage compensate by doubling the transcription of most X-linked genes (1). The MSL 1 complex is required for this male-specific hypertranscription (2,3).…”

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confidence: 99%

Recruitment of the Male-specific Lethal (MSL) Dosage Compensation Complex to an Autosomally Integrated roXChromatin Entry Site Correlates with an Increased Expression of an Adjacent Reporter Gene in Male Drosophila

Henry

Tews

et al. 2001

Journal of Biological Chemistry

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Drosophila dosage compensate (equalize X-linked gene products) by doubling the transcription of most X-linked genes in males. The MSL (male-specific lethal) ribonucleoprotein complex consisting of at least five proteins and two non-coding RNAs (roX1 and roX2) is essential for this transcription response. Recently it has been shown that the X-linked roX1 and roX2 genes each contain at least one chromatin entry site for the MSL complex. In this study we show that insertion of either roX1 or roX2 DNA sequences, upstream of an insulated lacZ reporter gene controlled with the constitutive armadillo promoter (arm-lacZ), results in a significant elevation of expression of lacZ in males. However, full compensation, that is a precise doubling of lacZ expression in males relative to females, was only observed in some lines carrying autosomal insertions of either roX1-arm-lacZ or roX2-arm-lacZ transgenes. Furthermore, we found that a 419-base pair fragment of roX1 that contains an MSL binding site was sufficient to cause a modest elevation of expression of lacZ in males, but this response was significantly less than obtained with a full-length roX1 cDNA. This is the first direct demonstration that insertion of an MSL chromatin entry site on an autosome results in elevated expression in males of genes near the entry site.In the vinegar fly Drosophila melanogaster, males have one X chromosome and females have two. Males dosage compensate by doubling the transcription of most X-linked genes (1). The MSL 1 complex is required for this male-specific hypertranscription (2, 3). The complex is comprised of at least five proteins, MSL1, MSL2, MSL3, MLE, and MOF and two non-coding RNAs, roX1 and roX2. All components of the complex co-localize to hundreds of sites along the male X chromosome (4 -6). Two of the proteins have enzymatic activity; MLE is an RNA helicase (7) and MOF is a histone acetylase (8). In addition, a kinase, JIL-1, preferentially associates with the male X chromosome (9), but it is not known if this protein is essential for dosage compensation. The complex only assembles in males as one of the components, MSL2, is not present in females (10 -12).The complex is initially targeted to the male X chromosome through binding to 30 -40 "high affinity" or "chromatin entry" sites (13). The complex is then thought to spread from these sites to other sites on the X chromosome (2). Two of these sites are the X-linked roX1 and roX2 genes (14). That is, the same genes that encode the RNA components of the complex also appear to contain DNA sequences that are recognized by the complex.It has recently been shown that a 217-bp DNA fragment of roX1 is sufficient to produce an ectopic chromatin entry site when inserted on an autosome (15).Previously, we developed an insulated reporter gene system to search for cis-acting X-linked DNA sequences that are required for dosage compensation (16). The system consists of the constitutive armadillo promoter driving expression of the lacZ reporter gene and flanked by SCS and SCSЈ insulator el...

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“…In Drosophila melanogaster, the initial signal for specification of the male or female state is the ratio of X chromosomes to autosomes. This signal is recognized and interpreted by an array of genes that act in sequence making the decisions ultimately leading to sexual differentiation (3,19,20,29,36,57). A considerable amount is now known regarding the molecular nature of some of these regulatory genes (2,4,28).…”

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confidence: 99%