Synergistic interactions between CLAMP and MSL complex facilitate Drosophila dosage compensation
Ontology highlight
ABSTRACT:
ORGANISM(S): Drosophila melanogaster
PROVIDER: GSE39271 | GEO | 2013/07/15
SECONDARY ACCESSION(S): PRJNA170445
REPOSITORIES: GEO
Similar Datasets
Project description:ChIP-seq and mRNA-seq experiments were performed to understand the role of the CLAMP protein in dosage compensation ChIP-seq experiments compared the binding profiles of CLAMP in male and female cells and mRNA-seq data to define the role of CLAMP in regulating genes on the X-chromosome
2013-07-15 | E-GEOD-39271 | biostudies-arrayexpress
Project description:Hi-C and 4C-seq anlaysis of Drosophila S2 cells Drosophila dosage compensation is an important model system for defining how active chromatin domains are formed. The Male-specific lethal dosage compensation complex (MSLc) increases transcript levels of genes along the length of the single male X-chromosome to equalize with that on the two female X-chromosomes. The strongest binding sites for MSLc cluster together in three-dimensional space independent of MSLc because clustering occurs in both sexes. CLAMP, a non-sex specific, ubiquitous zinc finger protein, binds synergistically with MSLc to enrich the occupancy of both factors on the male X-chromosome. Here, we demonstrate that CLAMP promotes the observed clustering of MSLc bindings sites. Genome-wide, CLAMP promotes interactions between active chromatin regions and represses interactions between inactive chromatin regions. Moreover, the X-enriched CLAMP protein promotes longer-range interactions on the active X-chromosome than autosomes. Overall, we define how long-range interactions, mediated by a locally-enriched ubiquitous transcription factor, generate a three-dimensional active chromatin domain.
2019-12-01 | GSE130544 | GEO
Project description:Hi-C and 4C-seq anlaysis of Drosophila S2 cells Drosophila dosage compensation is an important model system for defining how active chromatin domains are formed. The Male-specific lethal dosage compensation complex (MSLc) increases transcript levels of genes along the length of the single male X-chromosome to equalize with that on the two female X-chromosomes. The strongest binding sites for MSLc cluster together in three-dimensional space independent of MSLc because clustering occurs in both sexes. CLAMP, a non-sex specific, ubiquitous zinc finger protein, binds synergistically with MSLc to enrich the occupancy of both factors on the male X-chromosome. Here, we demonstrate that CLAMP promotes the observed clustering of MSLc bindings sites. Genome-wide, CLAMP promotes interactions between active chromatin regions and represses interactions between inactive chromatin regions. Moreover, the X-enriched CLAMP protein promotes longer-range interactions on the active X-chromosome than autosomes. Overall, we define how long-range interactions, mediated by a locally-enriched ubiquitous transcription factor, generate a three-dimensional active chromatin domain.
2019-12-01 | GSE130545 | GEO
Project description:Histone locus regulation by the Drosophila dosage compensation adaptor protein CLAMP
| PRJNA489269 | ENA
Project description:The Drosophila male-specific lethal (MSL) complex binds to the male X chromosome to activate transcription, and consists of five proteins, MSL1, MSL2, MSL3, MOF, MLE, and two roX RNAs. The MLE helicase remodels the roX lncRNAs, enabling the lncRNA-mediated assembly of the Drosophila dosage compensation complex. MSL2 is expressed only in males and interacts with the N-terminal zinc-finger of the transcription factor CLAMP that is important for specific recruitment of the MSL complex on the male X chromosome. Here we found that the unstructured C-terminal region of MLE interacts with 6-7 zinc-finger domains of CLAMP. In vitro 4-5 zinc fingers are critical for specific DNA-binding of CLAMP with GA-repeats, which constitute the core motif at the high affinity binding sites for MSL proteins. Deletion of the Clamp Binding Domain (CBD) in MLE results in decreasing of MSL proteins association with male X chromosome and increasing of male lethality. These results suggest that interactions of unstructured regions in MSL2 and MLE with CLAMP zinc finger domains are important for the specific recruitment of the MSL complex on the male X chromosome.
2024-03-20 | GSE239354 | GEO
Project description:The conserved histone locus body (HLB) assembles prior to zygotic gene activation early during development and concentrates factors into a nuclear domain of coordinated histone gene regulation. Although HLBs form specifically at replication dependent histone loci, the cis and trans factors that target HLB components to histone genes remained unknown. Here we report that conserved GA-repeat cis elements within the bidirectional histone3-histone4 promoter direct HLB formation in Drosophila. In addition, the CLAMP zinc-finger protein binds these GA-repeat motifs, increases chromatin accessibility, enhances histone gene transcription, and promotes HLB formation. We previously demonstrated that CLAMP also promotes the formation of another domain of coordinated gene regulation: the dosage-compensated male X-chromosome. Therefore, CLAMP binding to GA-repeat motifs promotes the formation of two distinct domains of coordinated gene activation located at different places in the genome.
2017-11-15 | GSE102922 | GEO
Project description:The conserved histone locus body (HLB) assembles prior to zygotic gene activation early during development and concentrates factors into a nuclear domain of coordinated histone gene regulation. Although HLBs form specifically at replication-dependent histone loci, the cis and trans factors that target HLB components to histone genes remained unknown. Here we report that conserved GA repeat cis elements within the bidirectional histone3-histone4 promoter direct HLB formation in Drosophila In addition, the CLAMP (chromatin-linked adaptor for male-specific lethal [MSL] proteins) zinc finger protein binds these GA repeat motifs, increases chromatin accessibility, enhances histone gene transcription, and promotes HLB formation. We demonstrated previously that CLAMP also promotes the formation of another domain of coordinated gene regulation: the dosage-compensated male X chromosome. Therefore, CLAMP binding to GA repeat motifs promotes the formation of two distinct domains of coordinated gene activation located at different places in the genome.
2018-09-05 | GSE119448 | GEO
Project description:The essential process of dosage compensation is required to equalize gene expression of X-chromosome genes between males (XY) and females (XX). In Drosophila, the conserved Male-specific lethal (MSL) histone acetyltransferase complex mediates dosage compensation by increasing transcript levels from genes on the single male X-chromosome approximately two-fold. Consistent with its increased levels of transcription, the male X-chromosome has enhanced chromatin accessibility, distinguishing it from the autosomes. Here, we demonstrate that the non-sex specific CLAMP (Chromatin-linked adaptor for MSL proteins) zinc finger protein that recognizes GA-rich sequences genome-wide promotes the specialized chromatin environment on the male X-chromosome. In contrast, MSL complex is not required for global male X-chromosome chromatin accessibility, and instead promotes chromatin accessibility just at its highest-occupancy sites. Overall, our results support a model where synergy between the global increases in accessibility promoted by CLAMP and the local effects of MSL complex create a specialized chromatin domain on the male X-chromosome.
2017-10-31 | GSE99893 | GEO
Project description:The essential process of dosage compensation is required to equalize gene expression of X-chromosome genes between males (XY) and females (XX). In Drosophila, the conserved Male-specific lethal (MSL) histone acetyltransferase complex mediates dosage compensation by increasing transcript levels from genes on the single male X-chromosome approximately two-fold. Consistent with its increased levels of transcription, the male X-chromosome has enhanced chromatin accessibility, distinguishing it from the autosomes. Here, we demonstrate that the non-sex specific CLAMP (Chromatin-linked adaptor for MSL proteins) zinc finger protein that recognizes GA-rich sequences genome-wide promotes the specialized chromatin environment on the male X-chromosome. In contrast, MSL complex is not required for global male X-chromosome chromatin accessibility, and instead promotes chromatin accessibility just at its highest-occupancy sites. Overall, our results support a model where synergy between the global increases in accessibility promoted by CLAMP and the local effects of MSL complex create a specialized chromatin domain on the male X-chromosome.
2017-10-31 | GSE99842 | 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