Genomes and Genes
Gene Symbol: mle
Alias: CG11680, Dmel\CG11680, MLE, Mle, mak, mll, mls, nap, nap[ts], maleless, CG11680-PA, CG11680-PC, male lethal, male-killer, male-lethal, maleless-no-action potential, mle-PA, mle-PC, no action potential, no-action-potential
Species: fruit fly
- Meller V, Gordadze P, Park Y, Chu X, Stuckenholz C, Kelley R, et al. Ordered assembly of roX RNAs into MSL complexes on the dosage-compensated X chromosome in Drosophila. Curr Biol. 2000;10:136-43 pubmed..We were able to immunoprecipitate roX2 RNA from male tissue-culture cells with antibodies to the proteins Msl1 and Mle, consistent with an integral association with MSL complexes...
- Aratani S, Kageyama Y, Nakamura A, Fujita H, Fujii R, Nishioka K, et al. MLE activates transcription via the minimal transactivation domain in Drosophila. Int J Mol Med. 2008;21:469-76 pubmed..Drosophila maleless (MLE), an ATPase/helicase, is a component of the DCC and essential for the viability of male flies...
- Belote J, Lucchesi J. Control of X chromosome transcription by the maleless gene in Drosophila. Nature. 1980;285:573-5 pubmed..Autoradiographic monitoring of RNA synthesis in larval polytene chromosomes of males homozygous for one of these mutations, mlets, reveals a significant reduction in the rate of X chromosome transcription. ..
- Furuhashi H, Nakajima M, Hirose S. DNA supercoiling factor contributes to dosage compensation in Drosophila. Development. 2006;133:4475-83 pubmed..These findings demonstrate that SCF plays a role in transcriptional activation via alteration of chromatin structure and provide evidence that SCF contributes to dosage compensation. ..
- Lee C, Hurwitz J. Human RNA helicase A is homologous to the maleless protein of Drosophila. J Biol Chem. 1993;268:16822-30 pubmed..among all known proteins of the DEAH family revealed that the highest homology was between RNA helicase A and the maleless protein (MLE) of Drosophila...
- Spierer A, Begeot F, Spierer P, Delattre M. SU(VAR)3-7 links heterochromatin and dosage compensation in Drosophila. PLoS Genet. 2008;4:e1000066 pubmed publisher..Taken together, these results bring to light a link between heterochromatin and dosage compensation...
- Gorman M, Franke A, Baker B. Molecular characterization of the male-specific lethal-3 gene and investigations of the regulation of dosage compensation in Drosophila. Development. 1995;121:463-75 pubmed..Two of the msls, the mle and msl-1 genes, encode proteins that are associated with hundreds of specific sites along the length of the male X ..
- Gladstein N, McKeon M, Horabin J. Requirement of male-specific dosage compensation in Drosophila females--implications of early X chromosome gene expression. PLoS Genet. 2010;6:e1001041 pubmed publisher..The key genes are male lethal and appear not to be required in females, or affect their viability...
- Dahlsveen I, Gilfillan G, Shelest V, Lamm R, Becker P. Targeting determinants of dosage compensation in Drosophila. PLoS Genet. 2006;2:e5 pubmed..Our bioinformatics analysis suggests that DCC binding sites may be composed of variable combinations of degenerate motifs. ..
- Greenberg A, Yanowitz J, Schedl P. The Drosophila GAGA factor is required for dosage compensation in males and for the formation of the male-specific-lethal complex chromatin entry site at 12DE. Genetics. 2004;166:279-89 pubmed..Here, we report that mutations in Trithorax-like (Trl) lead to the loss of a single chromatin entry site on the X, male lethality, and mislocalization of dosage compensation complexes. ..
- Larschan E, Alekseyenko A, Gortchakov A, Peng S, Li B, Yang P, et al. MSL complex is attracted to genes marked by H3K36 trimethylation using a sequence-independent mechanism. Mol Cell. 2007;28:121-33 pubmed..Our results support a model in which MSL complex uses high-affinity sites to initially recognize the X chromosome and then associates with many of its targets through sequence-independent features of transcribed genes. ..
- Kernan M, Kuroda M, Kreber R, Baker B, Ganetzky B. napts, a mutation affecting sodium channel activity in Drosophila, is an allele of mle, a regulator of X chromosome transcription. Cell. 1991;66:949-59 pubmed..tests, germline transformation, and analysis of mutations, that napts is a gain-of-function mutation of mle, a gene required for X chromosome dosage compensation and male viability...
- Prabhakaran M, Kelley R. A new strategy for isolating genes controlling dosage compensation in Drosophila using a simple epigenetic mosaic eye phenotype. BMC Biol. 2010;8:80 pubmed publisher..We focused our analysis on the modifier alleles of MSL1 and MLE (for 'maleless')...
- Cline T, Meyer B. Vive la différence: males vs females in flies vs worms. Annu Rev Genet. 1996;30:637-702 pubmed..Although no overlap has been found among the molecules used by flies and worms to achieve sex determination, striking similarities have been found in the genetic strategies used by these two species to differentiate their sexes. ..
- Bashaw G, Baker B. The msl-2 dosage compensation gene of Drosophila encodes a putative DNA-binding protein whose expression is sex specifically regulated by Sex-lethal. Development. 1995;121:3245-58 pubmed..MSL-2 protein is not produced in females and sequences in both the 5' and 3' UTRs are important for this sex-specific regulation. Furthermore, msl-2 pre-mRNA is alternatively spliced in a Sex-lethal-dependent fashion in its 5' UTR. ..
- Lee C, Chang K, Kuroda M, Hurwitz J. The NTPase/helicase activities of Drosophila maleless, an essential factor in dosage compensation. EMBO J. 1997;16:2671-81 pubmedDrosophila maleless (mle) is required for X chromosome dosage compensation and is essential for male viability...
- Rattner B, Meller V. Drosophila male-specific lethal 2 protein controls sex-specific expression of the roX genes. Genetics. 2004;166:1825-32 pubmed..We propose that this mechanism maintains a stable MSL/roX ratio that is favorable for localization of the complex to the X chromosome. ..
- Uenoyama T, Fukunaga A, Ioshi K. Studies on the sex-specific lethals of Drosophila melanogaster. V. Sex transformation caused by interactions between a female-specific lethal, Sxlf 1, and the male-specific lethals mle(3)132, msl-2(27), and mle. Genetics. 1982;102:233-43 pubmedInteractions between a female-specific lethal mutant, Sxlf 1, and each of three male-specific lethal mutants, mle(3)132, msl-2(27) and mle, of Drosophila melanogaster were observed to produce morphological changes in various sexually ..
- Palmer M, Richman R, Richter L, Kuroda M. Sex-specific regulation of the male-specific lethal-1 dosage compensation gene in Drosophila. Genes Dev. 1994;8:698-706 pubmed..Furthermore, the wild-type pattern of MSL-1 localization to the X chromosome is dependent on mle and msl-3 function, although a subset of sites are stained with MSL-1 antibodies in these mutants...
- Deng X, Meller V. Non-coding RNA in fly dosage compensation. Trends Biochem Sci. 2006;31:526-32 pubmed..Several recent studies in Drosophila provide new insight into the principles of X-chromosome recognition and the function of non-coding RNA in this process. ..
- Straub T, Becker P. Dosage compensation: the beginning and end of generalization. Nat Rev Genet. 2007;8:47-57 pubmed
- Mendjan S, Akhtar A. The right dose for every sex. Chromosoma. 2007;116:95-106 pubmed..Taken together, these findings suggest a role of the MSL complex in transcription elongation, RNA processing, and/or nuclear organization. ..
- Copps K, Richman R, Lyman L, Chang K, Rampersad Ammons J, Kuroda M. Complex formation by the Drosophila MSL proteins: role of the MSL2 RING finger in protein complex assembly. EMBO J. 1998;17:5409-17 pubmed publisher..are associated in immunoprecipitations, chromatographic steps and in the yeast two-hybrid system, but that the MLE protein is not tightly complexed in these assays...
- Izzo A, Regnard C, Morales V, Kremmer E, Becker P. Structure-function analysis of the RNA helicase maleless. Nucleic Acids Res. 2008;36:950-62 pubmedLoss of function of the RNA helicase maleless (MLE) in Drosophila melanogaster leads to male-specific lethality due to a failure of X chromosome dosage compensation...
- Stuckenholz C, Kageyama Y, Kuroda M. Guilt by association: non-coding RNAs, chromosome-specific proteins and dosage compensation in Drosophila. Trends Genet. 1999;15:454-8 pubmed..The discovery of non-coding RNAs that 'paint' dosage-compensated X chromosomes in mammals and in Drosophila suggests that RNAs play an intriguing, unexpected role in the regulation of chromatin structure and gene expression. ..
- Kageyama Y, Mengus G, Gilfillan G, Kennedy H, Stuckenholz C, Kelley R, et al. Association and spreading of the Drosophila dosage compensation complex from a discrete roX1 chromatin entry site. EMBO J. 2001;20:2236-45 pubmed..When inserted on autosomes, this small roX1 segment is sufficient to produce an ectopic chromatin entry site that can nucleate binding and spreading of the MSL complex hundreds of kilobases into neighboring regions. ..
- Bai X, Alekseyenko A, Kuroda M. Sequence-specific targeting of MSL complex regulates transcription of the roX RNA genes. EMBO J. 2004;23:2853-61 pubmed..Surprisingly, the DHS is not required for initiation of cis spreading of MSL complex, instead local transcription of roX RNAs correlates with extensive spreading. ..
- Straub T, Dahlsveen I, Becker P. Dosage compensation in flies: mechanism, models, mystery. FEBS Lett. 2005;579:3258-63 pubmed..We discuss the prevalent models in the context of recent experimental observations. ..
- Kind J, Akhtar A. Cotranscriptional recruitment of the dosage compensation complex to X-linked target genes. Genes Dev. 2007;21:2030-40 pubmed..We propose a model of dynamic MSL complex binding to active genes based on exposed DNA target elements. ..
- Bachiller D, Sanchez L. Mutations affecting dosage compensation in Drosophila melanogaster: effects in the germline. Dev Biol. 1986;118:379-84 pubmed..These mutations are the male-specific lethals msl-1, msl-2, and mle, which have been analyzed in the somatic tissues. Our aim was to know whether these mutations affect the germline...
- Stenberg P, Larsson J. Buffering and the evolution of chromosome-wide gene regulation. Chromosoma. 2011;120:213-25 pubmed publisher..In this review, we discuss the origin and function of buffering and compensation using Drosophila as a model. ..
- Straub T, Zabel A, Gilfillan G, Feller C, Becker P. Different chromatin interfaces of the Drosophila dosage compensation complex revealed by high-shear ChIP-seq. Genome Res. 2013;23:473-85 pubmed publisher..We present ChIP-seq binding profiles for all complex subunits, including the first description of the RNA helicase MLE binding pattern...
- Fukunaga A, Tanaka A, Oishi K. Maleless, a recessive autosomal mutant of Drosophila melanogaster that specifically kills male zygotes. Genetics. 1975;81:135-41 pubmedA second chromosome male-specific lethal gene, maleless (mle), in D. melanogaster is described. It kills males but not females in homozygous condition, regardless of whether female parents are heterozygous or homozygous for mle...
- Chang K, Kuroda M. Modulation of MSL1 abundance in female Drosophila contributes to the sex specificity of dosage compensation. Genetics. 1998;150:699-709 pubmed..Overcoming these control mechanisms by overexpressing both MSL1 and MSL2 in females results in 100% female-specific lethality. ..
- Li F, Parry D, Scott M. The amino-terminal region of Drosophila MSL1 contains basic, glycine-rich, and leucine zipper-like motifs that promote X chromosome binding, self-association, and MSL2 binding, respectively. Mol Cell Biol. 2005;25:8913-24 pubmed publisher..We propose that the basic region may mediate DNA binding and that the glycine-rich region may promote the association of MSL complexes to closely adjacent sites on the X chromosome...
- Bone J, Kuroda M. Dosage compensation regulatory proteins and the evolution of sex chromosomes in Drosophila. Genetics. 1996;144:705-13 pubmed..Our results support a model in which cis-acting regulatory sites for dosage compensation evolve on a neo-X chromosome arm in response to the degeneration of its former homologue. ..
- Amrein H, Axel R. Genes expressed in neurons of adult male Drosophila. Cell. 1997;88:459-69 pubmed..Our data suggest that the multimeric complex of dosage compensation proteins may operate in different ways on different sets of X-linked genes. ..
- Reenan R, Hanrahan C, Ganetzky B. The mle(napts) RNA helicase mutation in drosophila results in a splicing catastrophe of the para Na+ channel transcript in a region of RNA editing. Neuron. 2000;25:139-49 pubmed..Although maleless (mle) encodes a double-stranded RNA (dsRNA) helicase, exactly how mle(napts) affects para expression remained ..
- Franke A, Dernburg A, Bashaw G, Baker B. Evidence that MSL-mediated dosage compensation in Drosophila begins at blastoderm. Development. 1996;122:2751-60 pubmed..Other results show that the maleless (MLE) protein on embryo and larval chromosomes differs in its reactivity with antibodies; the functional ..
- Scott M, Pan L, Cleland S, Knox A, Heinrich J. MSL1 plays a central role in assembly of the MSL complex, essential for dosage compensation in Drosophila. EMBO J. 2000;19:144-55 pubmed..The MSL1 C-terminal domain shows similarity to a region of mouse CBP, a transcription co-activator. We conclude that a main role of MSL1 is to serve as the backbone for assembly of the MSL complex. ..
- Nusinow D, Panning B. Recognition and modification of seX chromosomes. Curr Opin Genet Dev. 2005;15:206-13 pubmed..Finally, evidence from mammals suggests that the chromatin modifications that mediate dosage compensation are very dynamic, because they are established, reversed and re-established early in development. ..
- Lee C, Reichman T, Baik T, Mathews M. MLE functions as a transcriptional regulator of the roX2 gene. J Biol Chem. 2004;279:47740-5 pubmed..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...
- Zhou S, Yang Y, Scott M, Pannuti A, Fehr K, Eisen A, et al. Male-specific lethal 2, a dosage compensation gene of Drosophila, undergoes sex-specific regulation and encodes a protein with a RING finger and a metallothionein-like cysteine cluster. EMBO J. 1995;14:2884-95 pubmed..At least four regulatory genes are required for this process. Three of these genes, maleless (mle), male-specific lethal 1 (msl-1) and male-specific lethal 3 (msl-3), have been cloned and their products ..
- Park S, Kang Y, Sypula J, Choi J, Oh H, Park Y. An evolutionarily conserved domain of roX2 RNA is sufficient for induction of H4-Lys16 acetylation on the Drosophila X chromosome. Genetics. 2007;177:1429-37 pubmed
- Akhtar A, Zink D, Becker P. Chromodomains are protein-RNA interaction modules. Nature. 2000;407:405-9 pubmed..In vitro analyses of the MOF and MSL-3 chromodomains indicate that these chromodomains may function as RNA interaction modules. Their interaction with non-coding RNA may target regulators to specific chromosomal sites. ..
- Meller V. Initiation of dosage compensation in Drosophila embryos depends on expression of the roX RNAs. Mech Dev. 2003;120:759-67 pubmed..Maternally provided MLE (Maleless) is required for roX1 stability. By contrast, roX2 is male-specific and is first observed at 6 h...
- Lyman L, Copps K, Rastelli L, Kelley R, Kuroda M. Drosophila male-specific lethal-2 protein: structure/function analysis and dependence on MSL-1 for chromosome association. Genetics. 1997;147:1743-53 pubmed..We found that MSL-2 binds in a reproducible, partial pattern to the male X chromosome in the absence of MLE or MSL-3, or when ectopically expressed at a low level in females...
- Bone J, Lavender J, Richman R, Palmer M, Turner B, Kuroda M. Acetylated histone H4 on the male X chromosome is associated with dosage compensation in Drosophila. Genes Dev. 1994;8:96-104 pubmed..The proteins encoded by two of these genes, maleless (mle) and male-specific lethal-1 (msl-1), are found associated with the X chromosome in males, suggesting that ..
- Marin I, Siegal M, Baker B. The evolution of dosage-compensation mechanisms. Bioessays. 2000;22:1106-14 pubmed..Some tantalizing similarities in the fly and mammalian mechanisms, however, remain to be explained. ..
- Kelley R, Meller V, Gordadze P, Roman G, Davis R, Kuroda M. Epigenetic spreading of the Drosophila dosage compensation complex from roX RNA genes into flanking chromatin. Cell. 1999;98:513-22 pubmed..The male X chromosome is also coated with noncoding roX RNAs. When either msl3, mle, or mof is mutant, a partial MSL complex is bound at only approximately 35 unusual sites distributed along the X...
- Meller V, Rattner B. The roX genes encode redundant male-specific lethal transcripts required for targeting of the MSL complex. EMBO J. 2002;21:1084-91 pubmed..Therefore, the roX1 and roX2 genes produce redundant, male-specific lethal transcripts required for targeting the MSL complex. ..
- Hamada F, Park P, Gordadze P, Kuroda M. Global regulation of X chromosomal genes by the MSL complex in Drosophila melanogaster. Genes Dev. 2005;19:2289-94 pubmed..We found that expression of many genes from the X chromosome decreased, while expression from the autosomes was largely unchanged. We conclude that the primary role of the MSL complex is to up-regulate the male X chromosome. ..
- Akhtar A. Dosage compensation: an intertwined world of RNA and chromatin remodelling. Curr Opin Genet Dev. 2003;13:161-9 pubmed..Furthermore, non-coding RNAs appear to play a dual role, being targeting modules as well as encoding for target sites for complex recognition. ..
- Rastelli L, Kuroda M. An analysis of maleless and histone H4 acetylation in Drosophila melanogaster spermatogenesis. Mech Dev. 1998;71:107-17 pubmedb>Maleless (mle) is essential in Drosophila melanogaster males both in somatic cells and in germ cells. In somatic cells mle is necessary for X-chromosome dosage compensation. The role of mle in the germline is unknown...
- Franke A, Baker B. Dosage compensation rox!. Curr Opin Cell Biol. 2000;12:351-4 pubmed
- Buscaino A, Kocher T, Kind J, Holz H, Taipale M, Wagner K, et al. MOF-regulated acetylation of MSL-3 in the Drosophila dosage compensation complex. Mol Cell. 2003;11:1265-77 pubmed..We propose that regulated acetylation of MSL-3 may provide a mechanistic explanation for spreading of the dosage compensation complex along the male X chromosome. ..
- Li F, Schiemann A, Scott M. Incorporation of the noncoding roX RNAs alters the chromatin-binding specificity of the Drosophila MSL1/MSL2 complex. Mol Cell Biol. 2008;28:1252-64 pubmed..We suggest that incorporation of the roX RNAs into the MSL complex alters the binding specificity of the chromatin-binding module formed by the amino-terminal domains of MSL1 and MSL2. ..
- Deng X, Meller V. roX RNAs are required for increased expression of X-linked genes in Drosophila melanogaster males. Genetics. 2006;174:1859-66 pubmed..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. ..
- Hilfiker A, Hilfiker Kleiner D, Pannuti A, Lucchesi J. mof, a putative acetyl transferase gene related to the Tip60 and MOZ human genes and to the SAS genes of yeast, is required for dosage compensation in Drosophila. EMBO J. 1997;16:2054-60 pubmed
- Morra R, Smith E, Yokoyama R, Lucchesi J. The MLE subunit of the Drosophila MSL complex uses its ATPase activity for dosage compensation and its helicase activity for targeting. Mol Cell Biol. 2008;28:958-66 pubmed..protein subunits that includes a histone acetyltransferase (MOF) and an ATP-dependent DEXH box RNA/DNA helicase (MLE)...
- Meller V. Dosage compensation: making 1X equal 2X. Trends Cell Biol. 2000;10:54-9 pubmed..Each organism uses a largely non-overlapping set of molecules to achieve the same outcome: 1X = 2X. ..
- Rastelli L, Richman R, Kuroda M. The dosage compensation regulators MLE, MSL-1 and MSL-2 are interdependent since early embryogenesis in Drosophila. Mech Dev. 1995;53:223-33 pubmedWe have analyzed the expression pattern and localization of MLE, MLS-1, MSL-2, and histone H4Ac16 during embryogenesis to determine when msl-dependent dosage compensation begins...
- Gu W, Wei X, Pannuti A, Lucchesi J. Targeting the chromatin-remodeling MSL complex of Drosophila to its sites of action on the X chromosome requires both acetyl transferase and ATPase activities. EMBO J. 2000;19:5202-11 pubmed..activities of two complex components, the histone acetyltransferase activity of MOF and the ATPase activity of MLE, may have in the targeting and association of the complex with the X chromosome...
- Smith E, Pannuti A, Gu W, Steurnagel A, Cook R, Allis C, et al. The drosophila MSL complex acetylates histone H4 at lysine 16, a chromatin modification linked to dosage compensation. Mol Cell Biol. 2000;20:312-8 pubmed..We have partially purified a complex containing MSL1, -2, and -3, MOF, MLE, and roX2 RNA and demonstrated that it exclusively acetylates H4 at lysine 16 on nucleosomal substrates...
- Oh H, Park Y, Kuroda M. Local spreading of MSL complexes from roX genes on the Drosophila X chromosome. Genes Dev. 2003;17:1334-9 pubmed..Thus, the protein components can carry out all essential functions of dosage compensation, but roX RNAs facilitate the correct targeting of MSL complexes, in part by nucleation of spreading from their sites of synthesis. ..
- Gilfillan G, Dahlsveen I, Becker P. Lifting a chromosome: dosage compensation in Drosophila melanogaster. FEBS Lett. 2004;567:8-14 pubmed..Deciphering the principles of X chromosome recognition and the nature of the chromatin configuration, that allows fine-tuning of transcription, remain the most interesting challenges. ..
- Gu W, Szauter P, Lucchesi J. Targeting of MOF, a putative histone acetyl transferase, to the X chromosome of Drosophila melanogaster. Dev Genet. 1998;22:56-64 pubmed..The products of at least five genes, maleless (mle), male-specific lethal 1, 2, and 3 (msl-1, msl-2, msl-3) and males absent on the first (mof), are necessary ..
- Meller V, Wu K, Roman G, Kuroda M, Davis R. roX1 RNA paints the X chromosome of male Drosophila and is regulated by the dosage compensation system. Cell. 1997;88:445-57 pubmed..The novel regulation and subnuclear localization of roX1 RNAs makes them candidates for an RNA component of the dosage compensation machinery. ..