Visualization of Transvection in Living Drosophila Embryos

Lim, Bomyi; Heist, Tyler; Levine, Michael; Fukaya, Takashi

doi:10.1016/j.molcel.2018.02.029

Cited by 150 publications

(158 citation statements)

References 58 publications

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“…Using previously published ChIP-chip and ChIP-seq data , we found no association between pairing and any of the DNA-binding insulator proteins (BEAF, Su(Hw), CTCF, and GAF)( Fig. 4A-D), suggesting that complex combinations of bound insulators, rather than individual proteins, might contribute to homologous pairing or stabilize interactions between already paired TADs (Lim et al, 2018). Intriguingly, both Cp190 and Mod(mdg4), insulator co-factors that do not directly bind to DNA, were associated with pairing ( Fig.…”

Section: Examining the Relationship Between Pairing Chromatin Factormentioning

confidence: 77%

TADs pair homologous chromosomes to promote interchromosomal gene regulation

Viets

Sauria

Chernoff

et al. 2018

Preprint

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Homologous chromosomes colocalize to regulate gene expression in processes including genomic imprinting and X-inactivation, but the mechanisms driving these interactions are poorly understood. In Drosophila, homologous chromosomes pair throughout development, promoting an interchromosomal gene regulatory mechanism called transvection. Despite over a century of study, the molecular features that drive chromosome-wide pairing and transvection are unknown. Here, we find that the ability to pair with a homologous sequence is not a general feature of all loci, but is specific to "button" loci interspersed across the genome. Buttons are characterized by topologically associated domains (TADs), which drive pairing with their endogenous loci from multiple genomic locations. Using a button spanning the spineless gene as a paradigm, we find that pairing is necessary but not sufficient for transvection. spineless pairing and transvection are cell-type-specific, suggesting that local buttoning and unbuttoning regulates transvection efficiency between cell types. Together, our data support a model in which button loci bring homologous chromosomes together to facilitate cell-type-specific interchromosomal gene regulation.

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Section: Examining the Relationship Between Pairing Chromatin Factormentioning

confidence: 77%

TADs pair homologous chromosomes to promote interchromosomal gene regulation

Viets

Sauria

Chernoff

et al. 2018

Preprint

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“…Enhancers can be situated far away from the genes they regulate 1,4 . Although not always the case 5,6 , at many gene loci proximity between enhancers and promoters is thought to be essential for enhancer function and gene activation 7,8 . How these enhancer-promoter interactions are initiated and maintained is not clearly understood.…”

Section: Introductionmentioning

confidence: 99%

BET inhibition disrupts transcription but retains enhancer-promoter contact

Crump

Ballabio

Godfrey

et al. 2019

Preprint

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In higher eukaryotes, enhancers are DNA sequences that enable complex temporal and tissue-specific regulation of genes. Although it is not entirely clear how enhancer-promoter interactions can increase gene expression, this proximity has been observed in multiple systems at multiple loci and is thought to be essential for the maintenance of gene expression. The formation of phase condensates is thought to be an essential component of enhancer function. Here, we show that pharmacological targeting of cells with inhibitors of BET (Bromodomain and Extra-Terminal domain) proteins can have a strong impact on transcription but very little impact on enhancer-promoter interactions. Treatment with 1,6-hexanediol, which dissolves phase condensate structures and reduces BET and Mediator protein binding at enhancers, can also have a strong effect on gene transcription, without disrupting enhancer-promoter interactions. These results suggest that activation of transcription and maintenance of enhancerpromoter interactions are separable events. Our findings further suggest that enhancer-promoter interactions are not dependent on high levels of BRD4 (Bromodomain-containing protein 4) and Mediator, and are likely maintained by a complex set of factors including additional activator complexes and loop extrusion by CTCF/cohesin.

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“…One consequence of this is that factors modulating the levels of transcription can do so by changing either the frequency with which a burst occurs (measured by the gap between bursts) or the size of each burst (measured by changes in burst duration and/or amplitude). Since forced looping of the beta-globin enhancer to its promoter led to an increase in burst frequency (Bartman et al 2016), it has been proposed that transcription factors activate transcription by modulating enhancer-promoter interactions, and hence bursting frequency; although other studies suggest enhancer-promoter interactions are not the underlying basis of transcriptional bursting (Lim et al 2018;Chen et al 2018). Though the molecular origin of bursting remains unknown, bursting frequency rather than burst duration or amplitudes seems to be the major parameter modulated in different species and contexts (So et al 2011;Senecal et al 2014;Xu et al 2015;Desponds et al 2016;Padovan-Merhar et al 2015;Lammers et al 2018;Berrocal et al 2018).…”

Section: Introductionmentioning

confidence: 99%

Enhancer priming enables fast and sustained transcriptional responses to Notch signaling

Falo‐Sanjuan

Lammers

García

et al. 2018

Preprint

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Information from developmental signaling pathways must be accurately decoded to generate transcriptional outcomes. In the case of Notch, the intracellular domain (NICD) transduces the signal directly to the nucleus.How enhancers decipher NICD in the real time of developmental decisions is not known. Using the MS2/MCP system to visualize nascent transcripts in single cells in Drosophila embryos we reveal how two target enhancers read Notch activity to produce synchronized and sustained profiles of transcription. By manipulating the levels of NICD and altering specific motifs within the enhancers we uncover two key principles. First, increased NICD levels alter transcription by increasing duration rather than frequency of transcriptional bursts. Second, priming of enhancers by tissue-specific transcription factors is required for NICD to confer synchronized and sustained activity; in their absence, transcription is stochastic and bursty. The dynamic response of an individual enhancer to NICD thus differs depending on the cellular context.

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Visualization of Transvection in Living Drosophila Embryos

Cited by 150 publications

References 58 publications

TADs pair homologous chromosomes to promote interchromosomal gene regulation

TADs pair homologous chromosomes to promote interchromosomal gene regulation

BET inhibition disrupts transcription but retains enhancer-promoter contact

Enhancer priming enables fast and sustained transcriptional responses to Notch signaling

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