MSL2 reads DNA shape to distinguish X from autosome for dosage compensation
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ABSTRACT:
PROVIDER: PRJNA302262 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR2919810.fastq.gz | Fastqsanger.gz | |||
| SRR2919820.fastq.gz | Fastqsanger.gz | |||
| SRR2919830.fastq.gz | Fastqsanger.gz | |||
| SRR2919840.fastq.gz | Fastqsanger.gz | |||
| SRR2919850.fastq.gz | Fastqsanger.gz |
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Project description:The rules according to which transcription factors selectively bind only a small subset of genomic sites from a vast pool of similar sequences are not understood. One of the most challenging tasks in DNA recognition is posed by dosage compensation systems that require the unequivocal distinction between a sex chromosome and all autosomes. In Drosophila melanogaster the male-specific-lethal dosage compensation complex (MSL-DCC) doubles the transcription output of most genes on the X chromosome via chromatin modification, but the nature of this selectivity is not known. We now found that MSL2, the male-specific organizer of the DCC, uses two distinct DNA interaction surfaces to read out previously identified X chromosomal ‘high affinity sites’. Specificity is provided by the interaction of the CXC domain with a novel, X-specific motif defined by DNA sequence and shape features. By several criteria these ‘PionX sites’ are primary determinants of X chromosome identity.
2016-08-30 | GSE75030 | GEO
Project description:The rules according to which transcription factors selectively bind only a small subset of genomic sites from a vast pool of similar sequences are not understood. One of the most challenging tasks in DNA recognition is posed by dosage compensation systems that require the unequivocal distinction between a sex chromosome and all autosomes. In Drosophila melanogaster the male-specific-lethal dosage compensation complex (MSL-DCC) doubles the transcription output of most genes on the X chromosome via chromatin modification, but the nature of this selectivity is not known. We now found that MSL2, the male-specific organizer of the DCC, uses two distinct DNA interaction surfaces to read out previously identified X chromosomal ‘high affinity sites’. Specificity is provided by the interaction of the CXC domain with a novel, X-specific motif defined by DNA sequence and shape features. By several criteria these ‘PionX sites’ are primary determinants of X chromosome identity.
2016-08-30 | GSE75032 | GEO
Project description:The rules according to which transcription factors selectively bind only a small subset of genomic sites from a vast pool of similar sequences are not understood. One of the most challenging tasks in DNA recognition is posed by dosage compensation systems that require the unequivocal distinction between a sex chromosome and all autosomes. In Drosophila melanogaster the male-specific-lethal dosage compensation complex (MSL-DCC) doubles the transcription output of most genes on the X chromosome via chromatin modification, but the nature of this selectivity is not known. We now found that MSL2, the male-specific organizer of the DCC, uses two distinct DNA interaction surfaces to read out previously identified X chromosomal ‘high affinity sites’. Specificity is provided by the interaction of the CXC domain with a novel, X-specific motif defined by DNA sequence and shape features. By several criteria these ‘PionX sites’ are primary determinants of X chromosome identity.
2016-08-30 | GSE75031 | GEO
Project description:In females, inactivation of one X-chromosome balances the dosage of X-linked genes similar to males. In addition, transcriptional upregulation balances the dosage of genes expressed from the single active-X to the double copy of autosomes in both sexes. However, the factors and mechanisms involved in the maintenance of X-chromosome inactivation (XCI) and X to autosome dosage compensation remain poorly understood. In this study, we report the contribution of m6A RNA methylation in maintenance of XCI and X to autosome dosage compensation in early embryonic and extraembryonic lineages. In the study, we find that m6A RNA methylation has a minimal role to play in maintenance of silencing of the inactivated-X chromsoome in TSC, XEN and EpiSC . Moreover, we also show that the X-linked transcripts are less enriched with m6A than the autosomal transcripts suggesting its role in increased X-transcript stability and hence upregulation. In addition, surprisingly we observed that X-linked transcripts without m6A are fully dosage compensated than the transcripts with m6A which undergo partial X to autosome dosage compensation in TSC, XEN and EpiSC. Further, we also found that global depletion of m6A level in TSC, XEN and EpiSC has a minor effect on the X to autosome dosage balance implicating the minor contribution of m6A RNA methylation during early embryogenesis.
2026-03-04 | GSE295197 | GEO
Project description:In females, inactivation of one X-chromosome balances the dosage of X-linked genes similar to males. In addition, transcriptional upregulation balances the dosage of genes expressed from the single active-X to the double copy of autosomes in both sexes. However, the factors and mechanisms involved in the maintenance of X-chromosome inactivation (XCI) and X to autosome dosage compensation remain poorly understood. In this study, we report the contribution of m6A RNA methylation in maintenance of XCI and X to autosome dosage compensation in early embryonic and extraembryonic lineages. In the study, we find that m6A RNA methylation has a minimal role to play in maintenance of silencing of the inactivated-X chromsoome in TSC, XEN and EpiSC . Moreover, we also show that the X-linked transcripts are less enriched with m6A than the autosomal transcripts suggesting its role in increased X-transcript stability and hence upregulation. In addition, surprisingly we observed that X-linked transcripts without m6A are fully dosage compensated than the transcripts with m6A which undergo partial X to autosome dosage compensation in TSC, XEN and EpiSC. Further, we also found that global depletion of m6A level in TSC, XEN and EpiSC has a minor effect on the X to autosome dosage balance implicating the minor contribution of m6A RNA methylation during early embryogenesis.
2026-03-04 | GSE295196 | GEO
Project description:Metazoa evolved regulatory networks to balance the expression of their sex chromosomes. In Drosophila, males have a single gene-rich X chromosome, whereas females have two. Balanced X/autosome expression is essential for viability, and in male flies is achieved by activation of genes on the X through the male-specific-lethal (MSL) dosage compensation complex (DCC). This ribonucleoprotein assembly contains long, non-coding roX RNAs. To dissect the functional requirements of roX in a cell-based system, we deleted the roX2 gene in male S2 cells and selected two independent lines lacking detectable roX RNA. In the absence of roX, the remaining MSL protein complex was unable to associate with known or newly identified binding sites and thus failed to activate transcription. Surprisingly, the X/autosome expression ratio appeared nevertheless compensated. Cytogenetic and genomic analyses revealed that both roX-deficient cell populations had acquired additional X chromosomes. Apparently, chromosome gains due to mis-segregation made up for the loss of DCC-mediated dosage compensation. Interestingly, ectopic expression of full-length roX2, but not of shortened derivatives, fully restored DCC binding and normalized the karyotype. These findings illustrate that X chromosome dosage compensation is critical for viability even in cultured cells and provide a striking example of rapid evolution under stringent selection.
2026-02-26 | GSE320392 | GEO
Project description:In mammals, X-chromosomal genes are expressed from a single copy since males (XY) possess a single X chromosome, while females (XX) undergo X inactivation. To compensate for this reduction in dosage compared to two active copies of autosomes, it has been proposed that genes from the active X chromosome exhibit dosage compensation. However, the existence and mechanism of X-to-autosome dosage compensation are still under debate. Here, we show that X-chromosomal transcripts are reduced in m6A modifications and more stable compared to their autosomal counterparts. Acute depletion of m6A selectively stabilises autosomal transcripts, resulting in perturbed dosage compensation in mouse embryonic stem cells. We propose that higher stability of X-chromosomal transcripts is directed by lower levels of m6A, indicating that mammalian dosage compensation is partly regulated by epitranscriptomic RNA modifications.
| EGAS00001007112 | EGA
Project description:Metazoa evolved regulatory networks to balance the expression of their sex chromosomes. In Drosophila, males have a single gene-rich X chromosome, whereas females have two. Balanced X/autosome expression is essential for viability, and in male flies is achieved by activation of genes on the X through the male-specific-lethal (MSL) dosage compensation complex (DCC). This ribonucleoprotein assembly contains long, non-coding roX RNAs. To dissect the functional requirements of roX in a cell-based system, we deleted the roX2 gene in male S2 cells and selected two independent lines lacking detectable roX RNA. In the absence of roX, the remaining MSL protein complex was unable to associate with known or newly identified binding sites and thus failed to activate transcription. Surprisingly, the X/autosome expression ratio appeared nevertheless compensated. Cytogenetic and genomic analyses revealed that both roX-deficient cell populations had acquired additional X chromosomes. Apparently, chromosome gains due to mis-segregation made up for the loss of DCC-mediated dosage compensation. Interestingly, ectopic expression of full-length roX2, but not of shortened derivatives, fully restored DCC binding and normalized the karyotype. These findings illustrate that X chromosome dosage compensation is critical for viability even in cultured cells and provide a striking example of rapid evolution under stringent selection.
2026-02-26 | GSE320376 | GEO
Project description:Metazoa evolved regulatory networks to balance the expression of their sex chromosomes. In Drosophila, males have a single gene-rich X chromosome, whereas females have two. Balanced X/autosome expression is essential for viability, and in male flies is achieved by activation of genes on the X through the male-specific-lethal (MSL) dosage compensation complex (DCC). This ribonucleoprotein assembly contains long, non-coding roX RNAs. To dissect the functional requirements of roX in a cell-based system, we deleted the roX2 gene in male S2 cells and selected two independent lines lacking detectable roX RNA. In the absence of roX, the remaining MSL protein complex was unable to associate with known or newly identified binding sites and thus failed to activate transcription. Surprisingly, the X/autosome expression ratio appeared nevertheless compensated. Cytogenetic and genomic analyses revealed that both roX-deficient cell populations had acquired additional X chromosomes. Apparently, chromosome gains due to mis-segregation made up for the loss of DCC-mediated dosage compensation. Interestingly, ectopic expression of full-length roX2, but not of shortened derivatives, fully restored DCC binding and normalized the karyotype. These findings illustrate that X chromosome dosage compensation is critical for viability even in cultured cells and provide a striking example of rapid evolution under stringent selection.
2026-02-26 | GSE320378 | GEO
Project description:Haploinsufficiency and aneuploidy are two phenomena, where alteration of gene dosage causes severe cellular defects ultimately resulting in developmental failures and disease. One remarkable exception is the X chromosome, where copy number differences between males and females are buffered through the action of dosage compensation systems. In Drosophila, the Male-Specific Lethal complex (MSLc) mediates two-fold upregulation of the single male X chromosome via Histone H4 lysine 16 acetylation (H4K16ac). The evolutionary origin and conservation of this process orchestrated by MSL2, the only male-specific protein within the fly MSLc, have remained unclear. Here, we report that MSL2, in addition to its function on the X, targets dosage-sensitive autosomal genes involved in patterning and morphogenesis. We show that the precise regulation of these genes by MSL2 is required for proper development of the fly wing. This set of dosage sensitive genes maintained such regulation during evolution, as MSL2 binds and similarly regulates mouse orthologues via deposition of H4K16ac. We propose that MSL2-mediated H4K16ac is an evolutionarily conserved process mediating gene-by-gene dosage compensation across flies and mammals.
2018-06-29 | GSE109900 | GEO