M1BP cooperates with CP190 to activate transcription at TAD borders and promote chromatin insulator activity

Bag, Indira; Chen, Shue; Rosin, Leah F.; Yang, Chen; Liu, Chen-Yu; Yu, Guo-Yun; Lei, Elissa P.

doi:10.1101/2020.10.27.357533

Cited by 4 publications

(3 citation statements)

References 75 publications

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“…Images used for analyses of CTs and folding of Bombyx versus Drosophila chromosomes were from previously published studies (5,64). For nuclei analysis in pupal neurons, pupal brains were dissected and neurons were isolated by FACS as previously described (65).…”

Section: Drosophila Nuclear Analyses and Oligopaint Datamentioning

confidence: 99%

Dosage compensation in Bombyx mori is achieved by partial repression of both Z chromosomes in males

Rosin

Chen

Lei

2021

Preprint

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Interphase chromatin is organized precisely to facilitate accurate gene expression. The structure-function relationship of chromatin is epitomized in sex chromosome dosage compensation (DC), where sex-linked gene expression is balanced between males and females via sex-specific alterations to 3D chromosome structure. Studies in ZW-bearing species suggest that DC is absent or incomplete in most lineages except butterflies and moths, where male (ZZ) chZ expression is reduced by half to equal females (ZW). However, whether one chZ is inactivated (as in mammals) or both are partially repressed (as in C. elegans) is unknown. Using Oligopaints in the silkworm, Bombyx mori, we visualize autosome and chZ organization in somatic cells from both sexes for the first time. We find that B. mori interphase chromosomes are highly compact relative to Drosophila chromosomes. Importantly, we show that in B. mori males, both chZs are similar in size and shape and are more compact than autosomes or the female chZ after DC establishment, suggesting that both male chZs are partially and equally downregulated. We also find that in the early stages of DC, the female chZ repositions toward the nuclear center concomitant with increased Z-linked gene expression, revealing the first non-sequencing-based support for Ohno's hypothesis. These studies represent the first visualization of interphase genome organization and chZ structure in Lepidoptera. We uncover striking similarities between DC in B. mori and C. elegans, despite these lineages harboring evolutionarily distinct sex chromosomes (ZW/XY), suggesting convergent evolution of DC mechanisms and a possible role for holocentricity in DC evolution.

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Section: Drosophila Nuclear Analyses and Oligopaint Datamentioning

confidence: 99%

Dosage compensation in Bombyx mori is achieved by partial repression of both Z chromosomes in males

Rosin

Chen

Lei

2021

Preprint

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“…However, findings from this work shows insulator bodies possess more of LLPS features than they would for PPPS. The reliance of insulator bodies on Cp190 in particular is intriguing as all Drosophila insulator protein complexes contain Cp190 and is also highly enriched at TAD borders (139).…”

Section: Discussionmentioning

confidence: 99%

Drosophila insulator proteins exhibit in-vivo liquid-liquid phase separation properties

Amankwaa

Schoborg

Labrador

2022

Preprint

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Mounting evidence implicates liquid-liquid phase separation (LLPS), the condensation of biomolecules into liquid-like droplets in the formation and dissolution of membraneless intracellular organelles (MLOs). Eukaryotic cells utilize MLOs or condensates for various biological processes, including emergency signaling, spatiotemporal control over steady-state biochemical reactions and heterochromatin formation. Insulator proteins function as architectural elements involved in establishing independent domains of transcriptional activity within eukaryotic genomes. In Drosophila, insulator proteins coalesce to form nuclear foci known as insulator bodies in response to osmotic stress and during apoptosis. However, the mechanism through which insulator proteins assemble into bodies and whether these bodies confer any genome function are yet to be fully investigated. Here, we identify signatures of liquid-liquid phase separation by insulator bodies, including high disorder tendency in insulator proteins, scaffold-client dependent assembly, extensive fusion behavior, sphericity, and sensitivity to 1,6-hexanediol. We also show that the cohesin subunit Rad21 is a component of insulator bodies adding to the known insulator proteins and the histone variant γH2Av constituents. Our data suggest a concerted role of cohesin and insulator proteins in insulator body formation and under physiological conditions. We propose a mechanism whereby these architectural proteins modulate 3D genome organization through LLPS.

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“…M1BP binding motifs are found to be enriched at TAD boundaries [48]. Recently, M1BP was found to interact with insulator proteins, mainly CP190, but also Su(Hw) and Mod(mdg4), at TAD boundaries [49]. Depletion of M1BP correlates with genome compaction, which shows that M1BP plays a role in chromatin accessibility and genome organization [49].…”

Section: Insulator Proteins Involved In Tad Formation Regulation and Maintenancementioning

confidence: 99%

Multi-Scale Organization of the Drosophila melanogaster Genome

Peterson

Samuelson

Hanlon

2021

Genes

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Interphase chromatin, despite its appearance, is a highly organized framework of loops and bends. Chromosomes are folded into topologically associating domains, or TADs, and each chromosome and its homolog occupy a distinct territory within the nucleus. In Drosophila, genome organization is exceptional because homologous chromosome pairing is in both germline and somatic tissues, which promote interhomolog interactions such as transvection that can affect gene expression in trans. In this review, we focus on what is known about genome organization in Drosophila and discuss it from TADs to territory. We start by examining intrachromosomal organization at the sub-chromosome level into TADs, followed by a comprehensive analysis of the known proteins that play a key role in TAD formation and boundary establishment. We then zoom out to examine interhomolog interactions such as pairing and transvection that are abundant in Drosophila but rare in other model systems. Finally, we discuss chromosome territories that form within the nucleus, resulting in a complete picture of the multi-scale organization of the Drosophila genome.

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M1BP cooperates with CP190 to activate transcription at TAD borders and promote chromatin insulator activity

Cited by 4 publications

References 75 publications

Dosage compensation in Bombyx mori is achieved by partial repression of both Z chromosomes in males

Dosage compensation in Bombyx mori is achieved by partial repression of both Z chromosomes in males

Drosophila insulator proteins exhibit in-vivo liquid-liquid phase separation properties

Multi-Scale Organization of the Drosophila melanogaster Genome

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