roX1 RNA Paints the X Chromosome of Male Drosophila and Is Regulated by the Dosage Compensation System

Meller, Victoria H.; Wu, Kwok; Roman, Gregg; Kuroda, Mitzi I.; Davis, Ronald L.

doi:10.1016/s0092-8674(00)81885-1

Cited by 274 publications

(226 citation statements)

References 69 publications

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“…Three of these represent annotated computational RNA (CR) genes: CR32777, CR31972, and CR32957. CR32777 corresponds to roX1, which is ubiquitously expressed at the blastoderm stage, hence it represents a false positive (20,21). The other two potential noncoding RNAs were recently identified independently in two other studies, and although the expression of CR32957 could not be detected by in situ hybridization (22), CR31972 transcripts are detected in the mesoderm (ref.…”

Section: Resultsmentioning

confidence: 99%

Comprehensive identification of Drosophila dorsal–ventral patterning genes using a whole-genome tiling array

Biemar

Nix²,

Piel

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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Dorsal-ventral (DV) patterning of the Drosophila embryo is initiated by Dorsal, a sequence-specific transcription factor distributed in a broad nuclear gradient in the precellular embryo. Previous studies have identified as many as 70 protein-coding genes and one microRNA (miRNA) gene that are directly or indirectly regulated by this gradient. A gene regulation network, or circuit diagram, including the functional interconnections among 40 Dorsal target genes and 20 associated tissue-specific enhancers, has been determined for the initial stages of gastrulation. Here, we attempt to extend this analysis by identifying additional DV patterning genes using a recently developed whole-genome tiling array. This analysis led to the identification of another 30 proteincoding genes, including the Drosophila homolog of Idax, an inhibitor of Wnt signaling. In addition, remote 5 exons were identified for at least 10 of the Ϸ100 protein-coding genes that were missed in earlier annotations. As many as nine intergenic uncharacterized transcription units were identified, including two that contain known microRNAs, miR-1 and -9a. We discuss the potential functions of these recently identified genes and suggest that intronic enhancers are a common feature of the DV gene network.gene network ͉ microRNA ͉ noncoding RNA D orsal-ventral (DV) asymmetry is established by complex interactions of at least 17 maternal genes that produce a localized ligand, Spätzle (Spz), in ventral regions of the perivitelline matrix surrounding the early embryo. Spz induces Toll signaling and the subsequent formation of a broad nuclear gradient of the Dorsal (Dl) protein, the Drosophila homolog of NF-B (1). The Dl nuclear gradient establishes the territories of the prospective mesoderm, neuroectoderm, and dorsal ectoderm by activating or repressing zygotic gene expression in a concentration-dependent manner. Previous genetic screens, subtractive hybridization assays, and microarray analyses identified as many as 70 protein-coding genes that are differentially expressed across the DV axis of early embryos undergoing cellularization and the initial phases of gastrulation. Most of those DV patterning genes encode transcription factors or components of cell signaling pathways, and many are likely to be direct targets of the Dorsal gradient (2).The advent of whole-genome tiling arrays provides a unique opportunity to identify microRNAs (miRNAs) and other noncoding RNAs that are regulated by the Dl gradient. In addition, these arrays present several opportunities for gene discovery not provided by traditional microarray screens. First, significant genes can be identified by using lower signal-to-noise cutoff values, because neighboring transcription units (TUs) serve as internal controls for even subtle elevations in tissue-specific expression. Second, there is no bias introduced by gene prediction models for the identification of protein-coding sequences. Third, it is possible to identify tissue-specific splicing isoforms for genes that display ubiquitous tra...

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Section: Resultsmentioning

confidence: 99%

Comprehensive identification of Drosophila dorsal–ventral patterning genes using a whole-genome tiling array

Biemar

Nix²,

Piel

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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“…The roX1 ex6 , roX1 SMC17A , and roX2 mutations have been previously described (Meller et al 1997;Meller and Rattner 2002;Deng et al 2005).…”

Section: Methodsmentioning

confidence: 99%

roXRNAs Are Required for Increased Expression of X-Linked Genes inDrosophila melanogasterMales

Deng

Meller

2006

Genetics

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The male-specific lethal (MSL) ribonucleoprotein complex is necessary for equalization of X:A expression levels in Drosophila males, which have a single X chromosome. It binds selectively to the male X chromosome and directs acetylation of histone H4 at lysine 16 (H4Ac16), a modification linked to elevated transcription. roX1 and roX2 noncoding RNAs are essential but redundant components of this complex. Simultaneous removal of both roX RNAs reduces X localization of the MSL proteins and permits their ectopic binding to autosomal sites and the chromocenter. However, the MSL proteins still colocalize, and low levels of H4Ac16 are detected at ectopic sites of MSL binding and residual sites on the X chromosome of roX1 À roX2 À males. Microarray analysis was performed to reveal the effect of roX1 and roX2 elimination on X-linked and autosomal gene expression. Expression of the X chromosome is decreased by 26% in roX1 À roX2 À male larvae. Enhanced expression could not be detected at autosomal sites of MSL binding in roX1 À roX2 À males. These results implicate failure to compensate X-linked genes, rather than inappropriate upregulation of autosomal genes at ectopic sites of MSL binding, as the primary cause of male lethality upon loss of roX RNAs.

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“…The protein and RNA components of the DCC, and acetylated H4K16, colocalize on the male X at the limited resolution afforded by polytene chromosome immunofluorescence (Bone et al 1994;Meller et al 1997;Franke and Baker 1999). To examine their coincidence at higher resolution in nonpolytenized nuclei, we performed ChIP with antibodies raised against MSL1, MOF, and acetylated H4K16 in 12-to 14-h-old Drosophila embryos.…”

Section: The DCC and Acetylated H4k16 Are Found In Gene-rich Regionsmentioning

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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roX1 RNA Paints the X Chromosome of Male Drosophila and Is Regulated by the Dosage Compensation System

Cited by 274 publications

References 69 publications

Comprehensive identification of Drosophila dorsal–ventral patterning genes using a whole-genome tiling array

Comprehensive identification of Drosophila dorsal–ventral patterning genes using a whole-genome tiling array

roXRNAs Are Required for Increased Expression of X-Linked Genes inDrosophila melanogasterMales

Chromosome-wide gene-specific targeting of theDrosophiladosage compensation complex

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