The simultaneous interaction of MSL2 with CLAMP and DNA provides redundancy in the initiation of dosage compensation in Drosophila males

Tikhonova, Evgeniya; Fedotova, Anna; Bonchuk, Artem; Mogila, Vladic; Larschan, Erica; Georgiev, Pavel; Maksimenko, Oksana

doi:10.1242/dev.179663

Cited by 22 publications

(60 citation statements)

References 35 publications

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“…MSL2 contributes to the specific recognition of HASs through the direct binding of GAGA motifs (23) andinteractions with CLAMP(28,29). However, our results suggested that the protein-protein interactions mediated by the N-terminal domain of MSL1 are the most critical interactions that define the specific binding of MSL to the X chromosome.…”

mentioning

confidence: 84%

“…This model was based on the finding that the ectopic expression of the MSL2 protein in females induced the formation of the DCC on the X chromosome. In a previous study (29), we showed that MSL1 and MSL2 were specifically recruited to the X chromosome in transgenic females expressing MSL2 WT -3xFLAG under the control of the Ubi promoter (86Fb). Even heterozygous MSL2 wt /+ females displayed reduced viability relative to males.…”

Section: N-terminal Sequences Of Msl1 Are Critical For the Specific Rmentioning

confidence: 95%

“…CLAMP is an essential protein in Drosophila, expressed in both sexes, which binds thousands of GA-rich sequences genome-wide (25)(26)(27). CLAMP interacts directly with MSL2 and opens chromatin at the HAS, which promotes MSL complex recruitment (27)(28)(29). The CLAMP-interaction and CXC domains have partially redundant functions for the recruitment of the MSL complex to the X chromosome (29).…”

Section: Introductionmentioning

confidence: 99%

“…CLAMP interacts directly with MSL2 and opens chromatin at the HAS, which promotes MSL complex recruitment (27)(28)(29). The CLAMP-interaction and CXC domains have partially redundant functions for the recruitment of the MSL complex to the X chromosome (29). The inactivation of both domains in MSL2 strongly reduces but does not eliminate MSL association with the X chromosome, although this reduction correlates with the low viability of mutant males (29).…”

Section: Introductionmentioning

confidence: 99%

“…The CLAMP-interaction and CXC domains have partially redundant functions for the recruitment of the MSL complex to the X chromosome (29). The inactivation of both domains in MSL2 strongly reduces but does not eliminate MSL association with the X chromosome, although this reduction correlates with the low viability of mutant males (29). Thus, additional components of the MSL complex are likely primarily responsible for the specific recruitment of the DCC to the X chromosome.…”

Section: Introductionmentioning

confidence: 99%

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N-Terminus ofDrosophila MelanogasterMSL1 Is Critical for Dosage Compensation

Babosha

Klimenko

Tikhonova

et al. 2020

Preprint

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The male-specific lethal dosage compensation complex (MSL complex or 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. MSL2 is a single protein component of the DCC that is expressed only in males and is essential for the specific recruitment of the DCC to the high-affinity “entry” sites (HASs) on the X chromosome. MSL2, together with MSL1, forms the heterotetrameric DCC core. Here, we demonstrated that the N-terminal unstructured region of MSL1 interacts with many different DNA-binding proteins that contain clusters of the C2H2 zinc-finger domains. Amino acid deletions in the N-terminal region of MSL1 strongly affect the binding of the DCC to the HASs on the male X chromosome. However, the binding of MSL2 to autosomal promoters was unaffected by amino acid deletions in MSL1. Males expressing mutant variants of MSL1 died during the larvae stage, demonstrating the critical role played by the N-terminal region in DCC activity. Our results suggest that MSL1 interacts with a variety of DNA-binding proteins to increase the specificity of DCC recruitment to the male X chromosome.BulletsThe N-terminal region of MSL1 interacts with 14 C2H2-type zinc-finger DNA-binding proteinsThe N-terminus of MSL1 is critical for the specific recruitment of the MSL complex to the X chromosomeThe N-terminus of MSL1 is important for the binding of MSL2 to a small fraction of autosomal promoters

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mentioning

confidence: 84%

Section: N-terminal Sequences Of Msl1 Are Critical For the Specific Rmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

N-Terminus ofDrosophila MelanogasterMSL1 Is Critical for Dosage Compensation

Babosha

Klimenko

Tikhonova

et al. 2020

Preprint

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Histone locus bodies: a paradigm for how nuclear biomolecular condensates control cell cycle regulated gene expression

Geisler,

Kemp,

Duronio

2023

Nucleus

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Histone locus bodies (HLBs) are biomolecular condensates that assemble at replication-dependent (RD) histone genes in animal cells. These genes produce unique mRNAs that are not polyadenylated and instead end in a conserved 3’ stem loop critical for coordinated production of histone proteins during S phase of the cell cycle. Several evolutionarily conserved factors necessary for synthesis of RD histone mRNAs concentrate only in the HLB. Moreover, because HLBs are present throughout the cell cycle even though RD histone genes are only expressed during S phase, changes in HLB composition during cell cycle progression drive much of the cell cycle regulation of RD histone gene expression. Thus, HLBs provide a powerful opportunity to determine the cause-and-effect relationships between nuclear body formation and cell cycle regulated gene expression. In this review, we focus on progress during the last five years that has advanced our understanding of HLB biology.

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Cell-free genomics reveal intrinsic, cooperative and competitive determinants of chromatin interactions

Eggers

Becker

2021

Nucleic Acids Research

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Metazoan transcription factors distinguish their response elements from a large excess of similar sequences. We explored underlying principles of DNA shape read-out and factor cooperativity in chromatin using a unique experimental system. We reconstituted chromatin on Drosophila genomes in extracts of preblastoderm embryos, mimicking the naïve state of the zygotic genome prior to developmental transcription activation. We then compared the intrinsic binding specificities of three recombinant transcription factors, alone and in combination, with GA-rich recognition sequences genome-wide. For MSL2, all functional elements reside on the X chromosome, allowing to distinguish physiological elements from non-functional ‘decoy’ sites. The physiological binding profile of MSL2 is approximated through interaction with other factors: cooperativity with CLAMP and competition with GAF, which sculpts the profile by occluding non-functional sites. An extended DNA shape signature is differentially read out in chromatin. Our results reveal novel aspects of target selection in a complex chromatin environment.

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The simultaneous interaction of MSL2 with CLAMP and DNA provides redundancy in the initiation of dosage compensation in Drosophila males

Cited by 22 publications

References 35 publications

N-Terminus ofDrosophila MelanogasterMSL1 Is Critical for Dosage Compensation

N-Terminus ofDrosophila MelanogasterMSL1 Is Critical for Dosage Compensation

Histone locus bodies: a paradigm for how nuclear biomolecular condensates control cell cycle regulated gene expression

Cell-free genomics reveal intrinsic, cooperative and competitive determinants of chromatin interactions

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