siRNAs from an X-linked satellite repeat promote X-chromosome recognition in Drosophila melanogaster
Significance Modulation of X-linked gene expression is essential in organisms with XX females and XY males. Various strategies for global regulation of X chromosomes have been proposed, but all require highly selective recognition of X chromatin. How this is achieved is not understood. The siRNA pat...
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| Published in | Proceedings of the National Academy of Sciences - PNAS Vol. 111; no. 46; pp. 16460 - 16465 |
|---|---|
| Main Authors | , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
National Academy of Sciences
18.11.2014
National Acad Sciences |
| Subjects | |
| Online Access | Get full text |
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| Abstract | Significance Modulation of X-linked gene expression is essential in organisms with XX females and XY males. Various strategies for global regulation of X chromosomes have been proposed, but all require highly selective recognition of X chromatin. How this is achieved is not understood. The siRNA pathway contributes to X recognition in a well-studied Drosophila model. We now show that ectopic production of siRNA from a repetitive sequence that is limited to the X chromosome also promotes X recognition. Differential activities of X-linked repeats suggest a control region model, in which siRNA produced by a few repeats acts on widely distributed X-linked target sequences to promote selective recognition, and modification, of a single chromosome.
Highly differentiated sex chromosomes create a lethal imbalance in gene expression in one sex. To accommodate hemizygosity of the X chromosome in male fruit flies, expression of X-linked genes increases twofold. This is achieved by the male- specific lethal (MSL) complex, which modifies chromatin to increase expression. Mutations that disrupt the X localization of this complex decrease the expression of X-linked genes and reduce male survival. The mechanism that restricts the MSL complex to X chromatin is not understood. We recently reported that the siRNA pathway contributes to localization of the MSL complex, raising questions about the source of the siRNAs involved. The X-linked 1.688 g/cm ³ satellite related repeats (1.688 X repeats) are restricted to the X chromosome and produce small RNA, making them an attractive candidate. We tested RNA from these repeats for a role in dosage compensation and found that ectopic expression of single-stranded RNAs from 1.688 X repeats enhanced the male lethality of mutants with defective X recognition. In contrast, expression of double-stranded hairpin RNA from a 1.688 X repeat generated abundant siRNA and dramatically increased male survival. Consistent with improved survival, X localization of the MSL complex was largely restored in these males. The striking distribution of 1.688 X repeats, which are nearly exclusive to the X chromosome, suggests that these are cis -acting elements contributing to identification of X chromatin. |
|---|---|
| AbstractList | Modulation of X-linked gene expression is essential in organisms with XX females and XY males. Various strategies for global regulation of X chromosomes have been proposed, but all require highly selective recognition of X chromatin. How this is achieved is not understood. The siRNA pathway contributes to X recognition in a well-studied
Drosophila
model. We now show that ectopic production of siRNA from a repetitive sequence that is limited to the X chromosome also promotes X recognition. Differential activities of X-linked repeats suggest a control region model, in which siRNA produced by a few repeats acts on widely distributed X-linked target sequences to promote selective recognition, and modification, of a single chromosome.
Highly differentiated sex chromosomes create a lethal imbalance in gene expression in one sex. To accommodate hemizygosity of the X chromosome in male fruit flies, expression of X-linked genes increases twofold. This is achieved by the male- specific lethal (MSL) complex, which modifies chromatin to increase expression. Mutations that disrupt the X localization of this complex decrease the expression of X-linked genes and reduce male survival. The mechanism that restricts the MSL complex to X chromatin is not understood. We recently reported that the siRNA pathway contributes to localization of the MSL complex, raising questions about the source of the siRNAs involved. The X-linked 1.688 g/cm
3
satellite related repeats (1.688
X
repeats) are restricted to the X chromosome and produce small RNA, making them an attractive candidate. We tested RNA from these repeats for a role in dosage compensation and found that ectopic expression of single-stranded RNAs from 1.688
X
repeats enhanced the male lethality of mutants with defective X recognition. In contrast, expression of double-stranded hairpin RNA from a 1.688
X
repeat generated abundant siRNA and dramatically increased male survival. Consistent with improved survival, X localization of the MSL complex was largely restored in these males. The striking distribution of 1.688
X
repeats, which are nearly exclusive to the X chromosome, suggests that these are
cis
-acting elements contributing to identification of X chromatin. Highly differentiated sex chromosomes create a lethal imbalance in gene expression in one sex. To accommodate hemizygosity of the X chromosome in male fruit flies, expression of X-linked genes increases twofold. This is achieved by the male- specific lethal (MSL) complex, which modifies chromatin to increase expression. Mutations that disrupt the X localization of this complex decrease the expression of X-linked genes and reduce male survival. The mechanism that restricts the MSL complex to X chromatin is not understood. We recently reported that the siRNA pathway contributes to localization of the MSL complex, raising questions about the source of the siRNAs involved. The X-linked 1.688 g/cm(3) satellite related repeats (1.688(X) repeats) are restricted to the X chromosome and produce small RNA, making them an attractive candidate. We tested RNA from these repeats for a role in dosage compensation and found that ectopic expression of single-stranded RNAs from 1.688(X) repeats enhanced the male lethality of mutants with defective X recognition. In contrast, expression of double-stranded hairpin RNA from a 1.688(X) repeat generated abundant siRNA and dramatically increased male survival. Consistent with improved survival, X localization of the MSL complex was largely restored in these males. The striking distribution of 1.688(X) repeats, which are nearly exclusive to the X chromosome, suggests that these are cis-acting elements contributing to identification of X chromatin. Significance Modulation of X-linked gene expression is essential in organisms with XX females and XY males. Various strategies for global regulation of X chromosomes have been proposed, but all require highly selective recognition of X chromatin. How this is achieved is not understood. The siRNA pathway contributes to X recognition in a well-studied Drosophila model. We now show that ectopic production of siRNA from a repetitive sequence that is limited to the X chromosome also promotes X recognition. Differential activities of X-linked repeats suggest a control region model, in which siRNA produced by a few repeats acts on widely distributed X-linked target sequences to promote selective recognition, and modification, of a single chromosome. Highly differentiated sex chromosomes create a lethal imbalance in gene expression in one sex. To accommodate hemizygosity of the X chromosome in male fruit flies, expression of X-linked genes increases twofold. This is achieved by the male- specific lethal (MSL) complex, which modifies chromatin to increase expression. Mutations that disrupt the X localization of this complex decrease the expression of X-linked genes and reduce male survival. The mechanism that restricts the MSL complex to X chromatin is not understood. We recently reported that the siRNA pathway contributes to localization of the MSL complex, raising questions about the source of the siRNAs involved. The X-linked 1.688 g/cm ³ satellite related repeats (1.688 X repeats) are restricted to the X chromosome and produce small RNA, making them an attractive candidate. We tested RNA from these repeats for a role in dosage compensation and found that ectopic expression of single-stranded RNAs from 1.688 X repeats enhanced the male lethality of mutants with defective X recognition. In contrast, expression of double-stranded hairpin RNA from a 1.688 X repeat generated abundant siRNA and dramatically increased male survival. Consistent with improved survival, X localization of the MSL complex was largely restored in these males. The striking distribution of 1.688 X repeats, which are nearly exclusive to the X chromosome, suggests that these are cis -acting elements contributing to identification of X chromatin. Highly differentiated sex chromosomes create a lethal imbalance in gene expression in one sex. To accommodate hemizygosity of the X chromosome in male fruit flies, expression of X-linked genes increases twofold. This is achieved by the male- specific lethal (MSL) complex, which modifies chromatin to increase expression. Mutations that disrupt the X localization of this complex decrease the expression of X-linked genes and reduce male survival. The mechanism that restricts the MSL complex to X chromatin is not understood. We recently reported that the siRNA pathway contributes to localization of the MSL complex, raising questions about the source of the siRNAs involved. The X-linked 1.688 g/cm... satellite related repeats (1.688... repeats) are restricted to the X chromosome and produce small RNA, making them an attractive candidate. We tested RNA from these repeats for a role in dosage compensation and found that ectopic expression of single-stranded RNAs from 1.688... repeats enhanced the male lethality of mutants with defective X recognition. In contrast, expression of double-stranded hairpin RNA from a 1.688... repeat generated abundant siRNA and dramatically increased male survival. Consistent with improved survival, X localization of the MSL complex was largely restored in these males. The striking distribution of 1.688... repeats, which are nearly exclusive to the X chromosome, suggests that these are cis-acting elements contributing to identification of X chromatin. (ProQuest: ... denotes formulae/symbols omitted.) Highly differentiated sex chromosomes create a lethal imbalance in gene expression in one sex. To accommodate hemizygosity of the X chromosome in male fruit flies, expression of X-linked genes increases twofold. This is achieved by the male- specific lethal (MSL) complex, which modifies chromatin to increase expression. Mutations that disrupt the X localization of this complex decrease the expression of X-linked genes and reduce male survival. The mechanism that restricts the MSL complex to X chromatin is not understood. We recently reported that the siRNA pathway contributes to localization of the MSL complex, raising questions about the source of the siRNAs involved. The X-linked 1.688 g/cm ³ satellite related repeats (1.688 X repeats) are restricted to the X chromosome and produce small RNA, making them an attractive candidate. We tested RNA from these repeats for a role in dosage compensation and found that ectopic expression of single-stranded RNAs from 1.688 X repeats enhanced the male lethality of mutants with defective X recognition. In contrast, expression of double-stranded hairpin RNA from a 1.688 X repeat generated abundant siRNA and dramatically increased male survival. Consistent with improved survival, X localization of the MSL complex was largely restored in these males. The striking distribution of 1.688 X repeats, which are nearly exclusive to the X chromosome, suggests that these are cis -acting elements contributing to identification of X chromatin. Highly differentiated sex chromosomes create a lethal imbalance in gene expression in one sex. To accommodate hemizygosity of the X chromosome in male fruit flies, expression of X-linked genes increases twofold. This is achieved by the male-specific lethal (MSL) complex, which modifies chromatin to increase expression. Mutations that disrupt the X localization of this complex decrease the expression of X-linked genes and reduce male survival. The mechanism that restricts the MSL complex to X chromatin is not understood. We recently reported that the siRNA pathway contributes to localization of the MSL complex, raising questions about the source of the siRNAs involved. The X-linked 1.688 g/cm³ satellite related repeats (1.688X repeats) are restricted to the X chromosome and produce small RNA, making them an attractive candidate. We tested RNA from these repeats for a role in dosage compensation and found that ectopic expression of single-stranded RNAs from 1.688X repeats enhanced the male lethality of mutants with defective X recognition. In contrast expression of double-stranded hairpin RNA from a 1.688X repeat generated abundant siRNA and dramatically increased male survival. Consistent with improved survival, X localization of the MSL complex was largely restored in these males. The striking distribution of 1.688X repeats, which are nearly exclusive to the X chromosome, suggests that these are cis-acting elements contributing to identification of X chromatin. Highly differentiated sex chromosomes create a lethal imbalance in gene expression in one sex. To accommodate hemizygosity of the X chromosome in male fruit flies, expression of X-linked genes increases twofold. This is achieved by the male- specific lethal (MSL) complex, which modifies chromatin to increase expression. Mutations that disrupt the X localization of this complex decrease the expression of X-linked genes and reduce male survival. The mechanism that restricts the MSL complex to X chromatin is not understood. We recently reported that the siRNA pathway contributes to localization of the MSL complex, raising questions about the source of the siRNAs involved. The X-linked 1.688 g/cm(3) satellite related repeats (1.688(X) repeats) are restricted to the X chromosome and produce small RNA, making them an attractive candidate. We tested RNA from these repeats for a role in dosage compensation and found that ectopic expression of single-stranded RNAs from 1.688(X) repeats enhanced the male lethality of mutants with defective X recognition. In contrast, expression of double-stranded hairpin RNA from a 1.688(X) repeat generated abundant siRNA and dramatically increased male survival. Consistent with improved survival, X localization of the MSL complex was largely restored in these males. The striking distribution of 1.688(X) repeats, which are nearly exclusive to the X chromosome, suggests that these are cis-acting elements contributing to identification of X chromatin.Highly differentiated sex chromosomes create a lethal imbalance in gene expression in one sex. To accommodate hemizygosity of the X chromosome in male fruit flies, expression of X-linked genes increases twofold. This is achieved by the male- specific lethal (MSL) complex, which modifies chromatin to increase expression. Mutations that disrupt the X localization of this complex decrease the expression of X-linked genes and reduce male survival. The mechanism that restricts the MSL complex to X chromatin is not understood. We recently reported that the siRNA pathway contributes to localization of the MSL complex, raising questions about the source of the siRNAs involved. The X-linked 1.688 g/cm(3) satellite related repeats (1.688(X) repeats) are restricted to the X chromosome and produce small RNA, making them an attractive candidate. We tested RNA from these repeats for a role in dosage compensation and found that ectopic expression of single-stranded RNAs from 1.688(X) repeats enhanced the male lethality of mutants with defective X recognition. In contrast, expression of double-stranded hairpin RNA from a 1.688(X) repeat generated abundant siRNA and dramatically increased male survival. Consistent with improved survival, X localization of the MSL complex was largely restored in these males. The striking distribution of 1.688(X) repeats, which are nearly exclusive to the X chromosome, suggests that these are cis-acting elements contributing to identification of X chromatin. |
| Author | Coarfa, Cristian Meller, Victoria H. Xiao, Weimin Gunaratne, Preethi H. Menon, Debashish U. |
| Author_xml | – sequence: 1 givenname: Debashish U. surname: Menon fullname: Menon, Debashish U. – sequence: 2 givenname: Cristian surname: Coarfa fullname: Coarfa, Cristian – sequence: 3 givenname: Weimin surname: Xiao fullname: Xiao, Weimin – sequence: 4 givenname: Preethi H. surname: Gunaratne fullname: Gunaratne, Preethi H. – sequence: 5 givenname: Victoria H. surname: Meller fullname: Meller, Victoria H. |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/25368194$$D View this record in MEDLINE/PubMed |
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| Keywords | roX RNA siRNA X chromosome recognition dosage compensation epigenetics |
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| Snippet | Significance Modulation of X-linked gene expression is essential in organisms with XX females and XY males. Various strategies for global regulation of X... Highly differentiated sex chromosomes create a lethal imbalance in gene expression in one sex. To accommodate hemizygosity of the X chromosome in male fruit... Modulation of X-linked gene expression is essential in organisms with XX females and XY males. Various strategies for global regulation of X chromosomes have... |
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| SubjectTerms | Animals Animals, Genetically Modified Base Pairing Base Sequence Biological Sciences Chromatin Chromosome Mapping Chromosomes DNA, Satellite - genetics DNA-Binding Proteins - analysis Dosage Compensation, Genetic Drosophila Drosophila - classification Drosophila - genetics Drosophila melanogaster Drosophila melanogaster - embryology Drosophila melanogaster - genetics Drosophila melanogaster - growth & development Drosophila melanogaster - ultrastructure Drosophila Proteins - analysis Drosophila Proteins - genetics Drosophila Proteins - physiology Euchromatin - genetics Female females Gene expression Gene Expression Regulation, Developmental Genes Genes, Lethal Insects Larva Larvae Male Male animals males Molecular Sequence Data Nuclear Proteins - analysis Repetitive Sequences, Nucleic Acid Ribonucleic acid RNA RNA Interference RNA, Small Interfering - biosynthesis RNA, Small Interfering - genetics RNA, Small Interfering - pharmacology RNA, Small Interfering - physiology RNA-Binding Proteins - genetics RNA-Binding Proteins - physiology Sequence Alignment Sequence Homology, Nucleic Acid Sex chromosomes Small interfering RNA Species Specificity Survival analysis Tandem Repeat Sequences Transcription Factors - analysis Transcription Factors - genetics Transcription Factors - physiology Transgenes X chromosome X Chromosome - genetics |
| Title | siRNAs from an X-linked satellite repeat promote X-chromosome recognition in Drosophila melanogaster |
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