Chromosome topology guides the
            <i>Drosophila</i>
            Dosage Compensation Complex for target gene activation

Schauer, Tamás; Ghavi-Helm, Yad; Sexton, Tom; Albig, Christian; Regnard, Catherine; Cavalli, Giacomo; Furlong, Eileen E. M.; Becker, Peter B.

doi:10.15252/embr.201744292

Cited by 46 publications

(61 citation statements)

References 51 publications

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“…Second, the complex must spread to epigenetically marked active transcription units to disseminate the activating H4 acetylation . We and others suggested that this dissemination may involve dynamic interactions between chromosomal regions of primary binding and target genes in the active nuclear compartment . Our current study reveals that the DCC assembles at HAS already at the earliest developmental window we could interrogate by ChIP, but this binding does not immediately lead to maximal H4K16 acetylation.…”

Section: Resultsmentioning

confidence: 55%

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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Section: Resultsmentioning

confidence: 55%

Progressive dosage compensation during Drosophila embryogenesis is reflected by gene arrangement

Prayitno¹,

Schauer²,

Regnard³

et al. 2019

EMBO Reports

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“…Dosage compensation is genetically encoded on the X chromosome in the form of ~300 high affinity binding sites (HAS) for the DCC, which are also referred to as 'chromosomal entry sites' (CES). The current model poses that the DCC first interacts with HAS on the X chromosome and then transfers to active genes in its vicinity [(Schauer et al, 2017) and reviewed in (Kuroda et al, 2016;Samata and Akhtar, 2018)]. These genes are epigenetically marked by methylation of histone H3 at lysine 36 (H3K36me3), a mark that is placed co-transcriptionally.…”

Section: Introductionmentioning

confidence: 99%

Factor cooperation for chromosome discrimination in Drosophila

Albig

Tikhonova

Krause

et al. 2018

Preprint

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Transcription regulators select their genomic binding sites from a large pool of similar, non-functional sequences. Although general principles that allow such discrimination are known, the complexity of DNA elements often precludes a prediction of functional sites.The process of dosage compensation in Drosophila allows exploring the rules underlying binding site selectivity. The male-specific-lethal (MSL) Dosage Compensation Complex selectively binds to some 300 X-chromosomal 'High Affinity Sites' (HAS) containing GA-rich 'MSL recognition elements' (MREs), but disregards thousands of other MRE sequences in the genome. The DNA-binding subunit MSL2 alone identifies a subset of MREs, but fails to recognize most MREs within HAS. The 'Chromatin-linked adaptor for MSL proteins' (CLAMP) also interacts with many MREs genome-wide and promotes DCC binding to HAS. Using genome-wide DNA-immunoprecipitation we describe extensive cooperativity between both factors, depending on the nature of the binding sites. These are explained by physical interaction between MSL2 and CLAMP. In vivo, both factors cooperate to compete with nucleosome formation at HAS. The male-specific MSL2 thus synergises with a ubiquitous GA-repeat binding protein for refined X/autosome discrimination. KeywordsATAC-seq/ CLAMP/ DNA-immunoprecipitation/ Dosage compensation/ MSL2

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“…ChIP-seq on MNase-digested chromatin and sonicated chromatin was performed as previously described 45,87 . For spike-in ChIP-seq on MNase-digested chromatin in combination with mild sonication, S2 cells (~3*10 8 cells) after RNAi were harvested and cross-linked with 1% formaldehyde for 8 min by adding 1 mL 10× fixing solution (50 mM HEPES pH 8.0, 100 mM NaCl, 1 mM EDTA, 0.5 mM EGTA) with 10% formaldehyde [16% formaldehyde solution (w/v) methanol-fee (Thermo Fischer)] per 10 mL culture at RT.…”

Section: Methodsmentioning

confidence: 99%

JASPer controls interphase histone H3S10 phosphorylation by chromosomal kinase JIL-1 in Drosophila

Albig

Wang

Dann

et al. 2019

Preprint

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31In flies, the chromosomal kinase JIL-1 is responsible for most interphase histone H3S10 32 phosphorylation and has been proposed to protect active chromatin from acquiring 33 heterochromatic marks, like dimethylated histone H3K9 (H3K9me2) and HP1. Here, we show 34 that JIL-1's targeting to chromatin depends on a new PWWP domain-containing protein 35JASPer (JIL-1 Anchoring and Stabilizing Protein). The JASPer-JIL-1 (JJ)-complex is the 36 major form of the kinase in vivo and is targeted to active genes and telomeric transposons 37 via binding of the PWWP domain of JASPer to H3K36me3 nucleosomes. Put in place, the 38 complex modulates the transcriptional output. JIL-1 and JJ-complex depletion in cycling cells 39 lead to small changes in H3K9me2 distribution at active genes and telomeric transposons. 40Finally, we identified many new interactors of the endogenous JJ-complex and propose that 41 JIL-1 not only prevents heterochromatin formation, but also coordinates chromatin-based 42 regulation in the transcribed part of the genome. 43 Key Words: PWWP domain / histone phosphorylation / COMPASS / heterochromatin / BOD1 44 / Dpy-30L1 / Telomeres 45 46 Main text 47In mammals, several nuclear kinases contribute to phosphorylation of histone H3 at serine 48 10 (H3S10ph) in interphase, whereas in Drosophila melanogaster, the essential kinase JIL-1 49 is responsible for most of it 1 . The significance of interphase H3S10ph is often 50 underestimated because most H3S10 phosphorylation in asynchronous cell populations 51 stems from mitotic chromatin, where it is deployed by Aurora kinase B 2,3 . Originally, 52interphase H3S10ph has been associated, in combination with H3K9ac and H3K14ac, with 53 transcriptional activation of immediate early genes upon MAPK activation 4,5 . In Drosophila, 54interphase H3S10ph is enriched at the body of active genes 6 . In mammal, in the extreme 55 case of mouse embryonic stem cells (mESC), ~30% of the genome is enriched for H3S10ph 56 in interphase 7 . 57The current model is that JIL-1 protects euchromatin from heterochromatization 8 . According 58 to the phospho-methyl switch model for mitotic H3S10ph 9 , placing H3S10ph prevents H3K9 59 methylation and subsequent binding of heterochromatin components. JIL-1 phosphorylates 60 various H3 peptides with different methylation states, including H3K9me2/3, with a 61 comparable efficiency 6 , whereas histone methyltransferases of the Su(var)3-9 family are 62 inhibited by H3S10ph 10,11 . Several observations suggest that JIL-1 is important for the 63 balance between eu-and heterochromatin. The Su(var)3-1 alleles of JIL-1 gene, which lead 64 to the expression of JIL-1 truncated in its C-terminal domain (CTD), result in reduced 65 heterochromatin spreading at euchromatin-heterochromatin boundaries 12,13 . Conversely, in 66 the JIL-1 z2/z2 null mutant, heterochromatin components spread into euchromatin. The 67 spreading of H3K9me2 and HP1 is highest on the euchromatic part of the X chromosome in 68 both sexes 14 , the spreading of the 7-zinc-finger pr...

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Chromosome topology guides the Drosophila Dosage Compensation Complex for target gene activation

Cited by 46 publications

References 51 publications

Progressive dosage compensation during Drosophila embryogenesis is reflected by gene arrangement

Progressive dosage compensation during Drosophila embryogenesis is reflected by gene arrangement

Factor cooperation for chromosome discrimination in Drosophila

JASPer controls interphase histone H3S10 phosphorylation by chromosomal kinase JIL-1 in Drosophila

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