Drosophila Male-Specific Lethal 2 Protein Controls Sex-Specific Expression of the roX Genes

Rattner, Barbara P.; Meller, Victoria H.

doi:10.1534/genetics.166.4.1825

Cited by 39 publications

(31 citation statements)

References 26 publications

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“…Two of the highaffinity sites correspond to the loci for roX1 and roX2 RNAs (Table 2, cytological positions 3F and 10C, respectively). Expression of these RNAs requires MSL-2 and their stability depends on their association to the DCC complex (Meller et al, 2000;Rattner and Meller, 2004). The fact that roX levels were similarly low in mutant and wild-type females supports the notion that msl-2 translational derepression in the mutant is only partial (see Fig.…”

Section: Discussionsupporting

confidence: 56%

Dual sex-specific functions ofDrosophilaUpstream of N-ras in the control of X chromosome dosage compensation

et al. 2009

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Dosage compensation in Drosophila melanogaster involves the assembly of the MSL-2-containing dosage compensation complex (DCC) on the single X chromosome of male flies. Translational repression of msl-2 mRNA blocks this process in females. Previous work indicated that the ubiquitous protein Upstream of N-ras (UNR) is a necessary co-factor for msl-2 repression in vitro. Here, we explore the function of UNR in vivo. Hypomorphic Unr mutant flies showed DCC assembly on high-affinity sites in the female X chromosomes, confirming that UNR inhibits dosage compensation in female flies. Unexpectedly, male mutant flies and UNRdepleted SL2 cells showed decreased DCC binding to the X chromosome, suggesting a role for UNR in DCC assembly or targeting. Consistent with this possibility, UNR overexpression resulted in moderate loss of DCC from the male X chromosome and predominant male lethality. Immunoprecipitation experiments revealed that UNR binds to roX1 and roX2, the non-coding RNA components of the DCC, providing possible targets for UNR function in males. These results uncover dual sex-specific functions of UNR in dosage compensation: to repress DCC formation in female flies and to promote DCC assembly on the male X chromosome.

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Section: Discussionsupporting

confidence: 56%

Dual sex-specific functions ofDrosophilaUpstream of N-ras in the control of X chromosome dosage compensation

et al. 2009

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“…While members of the DCC are interdependent in larvae, in early embryos maternally deposited MSL1 and MSL3 are present and stable prior to the zygotic expression of MSL2 at 3 h after egg laying. Similarly, roX transcripts are unstable in larvae lacking any MSL protein, but roX1 produced in early embryos is stable for several hours, even in the absence of MSL2 (Meller et al 1997;Meller 2003;Rattner and Meller 2004). roX1 is first transcribed .1 hr before dosage compensation is initiated, but just before heterochromatin becomes visible (Vlassova et al 1991;Lu et al 1998 ).…”

Section: Discussionmentioning

confidence: 99%

Coordinated Regulation of Heterochromatic Genes inDrosophila melanogasterMales

et al. 2009

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Dosage compensation modifies the chromatin of X-linked genes to assure equivalent expression in sexes with unequal X chromosome dosage. In Drosophila dosage compensation is achieved by increasing expression from the male X chromosome. The ribonucleoprotein dosage compensation complex (DCC) binds hundreds of sites along the X chromosome and modifies chromatin to facilitate transcription. Loss of roX RNA, an essential component of the DCC, reduces expression from X-linked genes. Surprisingly, loss of roX RNA also reduces expression from genes situated in proximal heterochromatin and on the small, heterochromatic fourth chromosome. Mutation of some, but not all, of the genes encoding DCC proteins produces a similar effect. Reduction of roX function suppresses position effect variegation (PEV), revealing functional alteration in heterochromatin. The effects of roX mutations on heterochromatic gene expression and PEV are limited to males. A sex-limited role for the roX RNAs in autosomal gene expression was unexpected. We propose that this reflects a difference in the heterochromatin of males and females, which serves to accommodate the heterochromatic Y chromosome present in the male nucleus. roX transcripts may thus participate in two distinct regulatory systems that have evolved in response to highly differentiated sex chromosomes: compensation of X-linked gene dosage and modulation of heterochromatin.

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“…MOF and MLE, as well as MSL3, require RNA for their localization to the X chromosome, and in turn, the roX RNAs are stabilized by the localization of the MSL complex to the X chromosome (2,8,40,46). In addition, transcription of roX RNAs is controlled by the MSL proteins (4,34,45). Together, these data uncover a series of interactions between components of the MSL complex that are required to ensure the complex's correct localization and activity.…”

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confidence: 93%

Zinc Finger Protein Zn72D Promotes Productive Splicing of the maleless Transcript

Worringer

Panning

2007

Molecular and Cellular Biology

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In organisms with sex chromosomes, dosage compensation equalizes gene expression between the sexes. In Drosophila melanogaster males, the male-specific lethal (MSL) complex of proteins and two noncoding roX RNAs coat the X chromosome, resulting in a twofold transcriptional upregulation to equalize gene expression with that of females. How MSL complex enrichment on the X chromosome is regulated is not well understood. We performed an RNA interference screen to identify new factors required for dosage compensation. Using a Drosophila Schneider S2 cell line in which green fluorescent protein (GFP)-tagged MSL2 localizes to the X chromosome, we assayed ϳ7,200 knockdowns for their effects on GFP-MSL2 distribution. One factor identified is the zinc finger protein Zn72D. In its absence, the MSL complex no longer coats the X chromosome. We demonstrate that Zn72D is required for productive splicing of the transcript for the MSL protein Maleless, explaining the dosage compensation defect. However, Zn72D is required for the viability of both sexes, indicating its functions are not sex specific. Consistent with this, Zn72D colocalizes with elongating RNA polymerase II, implicating it as a more general factor involved in RNA metabolism.

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Drosophila Male-Specific Lethal 2 Protein Controls Sex-Specific Expression of the roX Genes

Cited by 39 publications

References 26 publications

Dual sex-specific functions ofDrosophilaUpstream of N-ras in the control of X chromosome dosage compensation

Dual sex-specific functions ofDrosophilaUpstream of N-ras in the control of X chromosome dosage compensation

Coordinated Regulation of Heterochromatic Genes inDrosophila melanogasterMales

Zinc Finger Protein Zn72D Promotes Productive Splicing of the maleless Transcript

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