RNA‐dependent association of the <i>Drosophila</i> maleless protein with the male X chromosome

Richter, Liz; Bone, James R.; Kuroda, Mitzi I.

doi:10.1046/j.1365-2443.1996.26027.x

Cited by 94 publications

(85 citation statements)

References 33 publications

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“…Overexpressed Myc-MLE localized throughout the nucleus (Fig. 7A), consistent with the previous observation that overexpressed MLE localizes to all chromosomes in flies (46). MSL1 was still localized to the X chromosome in these Myc-MLE-overexpressing cells, indicating that the overexpressed protein did not interfere with MSL1 localization.…”

Section: Vol 27 2007supporting

confidence: 91%

“…For example, the acetyltransferase activity of MOF and the helicase and/or the ATPase function of MLE are both required for the complex to associate with the X chromosome in regions beyond the chromatin entry sites (21). 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).…”

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confidence: 99%

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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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Section: Vol 27 2007supporting

confidence: 91%

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confidence: 99%

Zinc Finger Protein Zn72D Promotes Productive Splicing of the maleless Transcript

Worringer

Panning

2007

Molecular and Cellular Biology

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“…In addition, MLE ATPase activity is dispensable for transcriptional activation supported by Prox2 (data not shown). These results are consistent with the findings that MLE retains X chromosome binding ability despite various mutations introduced in the ATPase motifs (26,36) and that ATPase activity is dispensable for transcriptional activation of the X-linked genes (37). Because mutations in the ATPase motifs of MLE affect the viability of male flies, the ATPase activity seems to be required for normal development of male flies (36).…”

Section: Discussionsupporting

confidence: 92%

MLE Functions as a Transcriptional Regulator of the roX2 Gene

Lee¹,

Reichman²,

Baik³

et al. 2004

Journal of Biological Chemistry

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Dosage compensation is a process that equalizes transcription activity between the sexes. In Drosophila, two non-coding RNA, roX1 and roX2, and at least six protein regulators, MSL-1, MSL-2, MSL-3, MLE, MOF, and JIL-1, have been identified as essential for dosage compensation. Although there is accumulating evidence of the intricate functional and physical interactions between protein and RNA regulators, little is known about how roX RNA expression and function are modulated in coordination with protein regulators. In this report, we have found that a relatively short (about 350 bp) upstream genomic region of the roX2 gene, Prox2, harbors an activity that drives transcription of the downstream gene. Our study has shown that MLE can stimulate the transcription activity of Prox2 and that MLE associates with Prox2 through direct interaction with a newly identified 54-bp repeat, Prox. Our observations suggest a novel mechanism by which roX2 RNA is regulated at the transcriptional level.

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“…Because both the MSL͞roX system in Drosophila and the Xist system in mammals rely on a noncoding RNA for function, it is striking that the POF protein includes a putative RNAbinding domain (RRM1). The chromosome-specific binding of POF is not sensitive to RNase treatment; however, binding of MSL1 and MSL2 is also resistant to this treatment (24). The functional relevance of the RNA-binding domain remains to be investigated.…”

Section: Discussionmentioning

confidence: 99%

“…A polyclonal affinity-purified hen IgY anti-POF was used as the primary antibody (1:100), and a donkey anti-rabbit antibody conjugated with Cy3 (Jackson Laboratories) was used as the secondary antibody (1:300). RNase treatment of salivary glands to test RNA dependence of POF binding was done according to described methods (24). Chromosomes were analyzed with a Zeiss Axiophot microscope equipped with a KAPPA DX3°C charge-coupled device camera.…”

Section: Methodsmentioning

confidence: 99%

Painting of fourth, a chromosome-specific protein inDrosophila

Larsson

Chen

Rasheva

et al. 2001

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

119

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Chromosome-specific gene regulation is known thus far only as a mechanism to equalize the transcriptional activity of the single male X chromosome with that of the two female X chromosomes. In Drosophila melanogaster, a complex including the five MaleSpecific Lethal (MSL) proteins, ''paints'' the male X chromosome, mediating its hypertranscription. Here, with the molecular cloning of Painting of fourth (Pof ), we describe a previously uncharacterized gene encoding a chromosome-specific protein in Drosophila. Unlike the MSL proteins, POF paints an autosome, the fourth chromosome of Drosophila melanogaster. Chromosome translocation analysis shows that the binding depends on an initiation site in the proximal region of chromosome 4 and spreads in cis to involve the entire chromosome. The spreading depends on sequences or structures specific to chromosome 4 and cannot extend to parts of other chromosomes translocated to the fourth. Spreading can also occur in trans to a paired homologue that lacks the initiation region. In the related species Drosophila busckii, POF paints the entire X chromosome exclusively in males, suggesting relationships between the fourth chromosome and the X and between POF complexes and dosage-compensation complexes.

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RNA‐dependent association of the Drosophila maleless protein with the male X chromosome

Cited by 94 publications

References 33 publications

Zinc Finger Protein Zn72D Promotes Productive Splicing of the maleless Transcript

Zinc Finger Protein Zn72D Promotes Productive Splicing of the maleless Transcript

MLE Functions as a Transcriptional Regulator of the roX2 Gene

Painting of fourth, a chromosome-specific protein inDrosophila

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