Factor cooperation for chromosome discrimination in <i>Drosophila</i>

Albig, Christian; Tikhonova, Evgeniya; Krause, Silke; Maksimenko, Oksana; Regnard, Catherine; Becker, Peter B.

doi:10.1101/414193

Cited by 9 publications

(30 citation statements)

References 73 publications

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“…3c). Importantly, the observed difference in APs binding at the B2 boundary genomic region in Kc167 cells is not due to differential chromatin accessibility since Kc167 and S2 cells show a remarkable similar ATAC-seq profile at the Notch locus 44 ( Supplementary Fig. 3b, c).…”

Section: Resultsmentioning

confidence: 87%

In situ dissection of domain boundaries affect genome topology and gene transcription in Drosophila

et al. 2020

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Chromosomes are organized into high-frequency chromatin interaction domains called topologically associating domains (TADs), which are separated from each other by domain boundaries. The molecular mechanisms responsible for TAD formation are not yet fully understood. In Drosophila, it has been proposed that transcription is fundamental for TAD organization while the participation of genetic sequences bound by architectural proteins (APs) remains controversial. Here, we investigate the contribution of domain boundaries to TAD organization and the regulation of gene expression at the Notch gene locus in Drosophila. We find that deletion of domain boundaries results in TAD fusion and long-range topological defects that are accompanied by loss of APs and RNA Pol II chromatin binding as well as defects in transcription. Together, our results provide compelling evidence of the contribution of discrete genetic sequences bound by APs and RNA Pol II in the partition of the genome into TADs and in the regulation of gene expression in Drosophila.

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Section: Resultsmentioning

confidence: 87%

In situ dissection of domain boundaries affect genome topology and gene transcription in Drosophila

et al. 2020

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“…To characterize the direct DNA binding of MSL2, DNA fragments from paired‐end sequencing runs were computationally subset to sizes between 10 and 130 bp, i.e., sub‐nucleosomal length, since it has been previously shown that HAS are nucleosome‐free . For clarity, we refer to those binding events as direct “DNA” binding (Fig A).…”

Section: Resultsmentioning

confidence: 99%

“…αMSL1, αMSL2, αMSL3, αMOF, and αMLE antibodies were previously described in Refs . αSXL antibody was kindly provided by F. Gebauer and previously described in Ref.…”

Section: Methodsmentioning

confidence: 99%

“…Key to targeting of the X are genetically encoded DCC binding sites, which are termed chromosomal entry sites (CES; ) or high‐affinity sites (HAS; ). DCC is targeted to the X through its DNA binding subunit, MSL2 , which cooperates with the ubiquitous CLAMP protein for tight binding to so‐called MSL response elements (MREs) . According to the current model, DCC “spreads” from HAS to transcriptionally active genes in the nuclear vicinity .…”

Section: Introductionmentioning

confidence: 99%

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Progressive dosage compensation during Drosophila embryogenesis is reflected by gene arrangement

Prayitno¹,

Schauer²,

Regnard³

et al. 2019

EMBO Reports

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In Drosophila melanogaster males, X‐chromosome monosomy is compensated by chromosome‐wide transcription activation. We found that complete dosage compensation during embryogenesis takes surprisingly long and is incomplete even after 10 h of development. Although the activating dosage compensation complex (DCC) associates with the X‐chromosome and MOF acetylates histone H4 early, many genes are not compensated. Acetylation levels on gene bodies continue to increase for several hours after gastrulation in parallel with progressive compensation. Constitutive genes are compensated earlier than developmental genes. Remarkably, later compensation correlates with longer distances to DCC binding sites. This time–space relationship suggests that DCC action on target genes requires maturation of the active chromosome compartment.

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“…Although the MSL2 component of MSLc has a low affinity for MREs, MSL complex requires synergy with an essential, non sex-specific, zinc finger adapter protein known as chromatinlinked adapter for MSL proteins (CLAMP) in order to stabilize its binding to MREs [19][20][21] .…”

Section: Introductionmentioning

confidence: 99%

The zinc finger protein CLAMP promotes long-range chromatin interactions that mediate dosage compensation of theDrosophilamale X-chromosome

Jordan

Larschan

2020

Preprint

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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. Moreover, the X-enriched CLAMP protein more strongly promotes longer-range interactions on the X-chromosome than autosomes. Genome-wide, CLAMP promotes interactions between active chromatin regions together with other insulator proteins. Overall, we define how long-range interactions which are modulated by a locally enriched ubiquitous transcription factor promote hyper-activation of the X-chromosome to mediate dosage compensation.

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Factor cooperation for chromosome discrimination in Drosophila

Cited by 9 publications

References 73 publications

In situ dissection of domain boundaries affect genome topology and gene transcription in Drosophila

In situ dissection of domain boundaries affect genome topology and gene transcription in Drosophila

Progressive dosage compensation during Drosophila embryogenesis is reflected by gene arrangement

The zinc finger protein CLAMP promotes long-range chromatin interactions that mediate dosage compensation of theDrosophilamale X-chromosome

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