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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Similar Datasets
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:This SuperSeries is composed of the SubSeries listed below.
2016-08-30 | GSE75033 | GEO
Project description:Confinement of the X chromosome into a territory for dosage compensation (DC) is a prime example of subnuclear compartmentalization for transcription regulation at the megabase scale. In D. melanogaster, two sex-specific non-coding (nc) RNAs roX1 and roX2 are transcribed from the X chromosome. They associate with the Male-specific lethal (MSL) complex, which by acetylating histone H4 lysine 16 (H4K16ac) confers approximately 2-fold upregulated expression of male X-linked genes. Current models explain X-over-autosome specificity based on the MSL2 subunit recognizing cis-regulatory DNA high-affinity sites (HAS). However, HAS motifs are also found on autosomes, indicating that additional factors have evolved to confer stable association of the MSL complex with the X. Here, we show that the low-complexity C-terminal domain (CTD) of MSL2 renders its recruitment to the X chromosome sensitive to roX ncRNAs. roX-MSL2-CTD form a stably condensated state, and functional analyses in Drosophila and mammalian cells reveal the critical importance of their interplay for DC in vivo. Replacing the CTD of mammalian MSL2 with that from Drosophila and expressing roX in cis is sufficient to nucleate ectopic DC in mammalian cells. Thus, the condensating nature of roX-MSL2CTD is the primary determinant for specific compartmentalization of the X in Drosophila.
2020-08-07 | GSE129795 | GEO
Project description:Confinement of the X chromosome into a territory for dosage compensation (DC) is a prime example of subnuclear compartmentalization for transcription regulation at the megabase scale. In D. melanogaster, two sex-specific non-coding (nc) RNAs roX1 and roX2 are transcribed from the X chromosome. They associate with the Male-specific lethal (MSL) complex, which by acetylating histone H4 lysine 16 (H4K16ac) confers approximately 2-fold upregulated expression of male X-linked genes. Current models explain X-over-autosome specificity based on the MSL2 subunit recognizing cis-regulatory DNA high-affinity sites (HAS). However, HAS motifs are also found on autosomes, indicating that additional factors have evolved to confer stable association of the MSL complex with the X. Here, we show that the low-complexity C-terminal domain (CTD) of MSL2 renders its recruitment to the X chromosome sensitive to roX ncRNAs. roX-MSL2-CTD form a stably condensated state, and functional analyses in Drosophila and mammalian cells reveal the critical importance of their interplay for DC in vivo. Replacing the CTD of mammalian MSL2 with that from Drosophila and expressing roX in cis is sufficient to nucleate ectopic DC in mammalian cells. Thus, the condensating nature of roX-MSL2CTD is the primary determinant for specific compartmentalization of the X in Drosophila.
2020-08-07 | GSE129796 | GEO
Project description:MSL (Male-specific lethal) complex increases transcription on the single X chromosome of Drosophila males in order to equalize expression of X-linked genes between males (XY) and females (XX). The increase in transcript levels correlates with MSL- dependent acetylation of histone H4 at K16 within the bodies of active genes, but identification of the transcriptional step affected has not been possible. In this study, we use global run-on sequencing (GRO-seq) to examine the specific effect of MSL complex on RNA Polymerase II (RNAP II) on a genome-wide level. Results indicate that MSL complex enhances transcription by facilitating the progression of RNAP II across the bodies of active X-linked genes. Improving transcriptional output downstream of typical gene-specific control may explain how dosage compensation can be imposed on the diverse set of genes along an entire chromosome. Global Run-On Sequencing (GRO-Seq) reads, i.e., RNA-Seq of nascent RNA transcripts, from D. Melanogaster SL2 cells. Two biological replicates of cells treated with control GFP RNAi and cells treated with MSL2 RNAi were analyzed.
2011-03-03 | E-GEOD-25887 | biostudies-arrayexpress
Project description:The male-specific dosage compensation complex (DCC), which consists of five proteins and two non-coding roX RNAs, is necessary for the transcriptional enhancement of X-linked genes to compensate for the sex chromosome monosomy in Drosophila XY males, compared with XX females. The MSL1 and MSL2 proteins form the heterotetrameric core of DCC and are critical for the specific recruitment of the DCC to the high-affinity “entry” sites (HAS) on the X chromosome. Here we demonstrated that the N-terminal region of MSL1 is critical for its stability and functions. Amino acid deletions and substitutions in the N-terminal region of MSL1 strongly affect both interaction with roX2 RNA and DCC binding to HAS on the X chromosome. In particular, substitution of the conserved N-terminal amino-acids 3-7 in MSL1GS has an affect on dosage compensation similar to inactivation of genes encoding roX RNAs. MSL1GS binds to promoters like MSL1WT but does not co-bind with MSL2 and MSL3 to X chromosomal HAS. However, over-expression of MSL2 partially restores the functional activity of MSL1GS in dosage compensation. Thus, the interaction of MSL1 with roX RNA is critical for the efficient assembly of DCCs on HAS of the male X chromosome.
2024-11-30 | GSE243396 | 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
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