Local Chromatin Motion and Transcription

Babokhov, Michael; Hibino, Kayo; Itoh, Yuji; Maeshima, Kazuhiro

doi:10.1016/j.jmb.2019.10.018

Cited by 34 publications

(21 citation statements)

References 76 publications

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“…6D ). This finding is consistent with the observation in our recent report that active Pol II globally constrains chromatin ( 27 , 28 , 41 ), suggesting that chromatin constraint by clusters/condensates of RNA polymerases may be a general mechanism for efficient transcription.…”

Section: Discussionsupporting

confidence: 93%

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Transcriptional suppression of ribosomal DNA with phase separation

et al. 2020

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The nucleolus is a nuclear body with multiphase liquid droplets for ribosomal RNA (rRNA) transcription. How rRNA transcription is regulated in the droplets remains unclear. Here, using single-molecule tracking of RNA polymerase I (Pol I) and chromatin-bound upstream binding factor (UBF), we reveal suppression of transcription with phase separation. For transcription, active Pol I formed small clusters/condensates that constrained rDNA chromatin in the nucleolus fibrillar center (FC). Treatment with a transcription inhibitor induced Pol I to dissociate from rDNA chromatin and to move like a liquid within the nucleolar cap that transformed from the FC. Expression of a Pol I mutant associated with a craniofacial disorder inhibited transcription by competing with wild-type Pol I clusters and transforming the FC into the nucleolar cap. The cap droplet excluded an initiation factor, ensuring robust silencing. Our findings suggest a mechanism of rRNA transcription suppression via phase separation of intranucleolar molecules governed by Pol I.

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Section: Discussionsupporting

confidence: 93%

“…As active Pol I is known to form clusters on active rDNA in the FC (24), as shown in fig. S3E, clustered active Pol I appears to constrain rDNA chromatin, which is consistent with observations of RNA Pol II (27,28,41) and the transcription factory model of RNA transcription (42,43).…”

Section: Pol I Constrains Rdna Chromatin Motionsupporting

confidence: 86%

Transcriptional suppression of ribosomal DNA with phase separation

et al. 2020

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“…At least for euchromatin, the published literature is full of cartoons, which imply a rather open configuration of chromatin loops. In contrast to an interchromatin space expanding both between and in the interior of open chromatin loops, the concept of the interchromatin compartment implies that chromatin loops and the resulting CDs may be compacted to an extent that the access of macromolecules, such as individual transcription factors and regulatory RNAs, can be largely constrained, while the access of macromolecular aggregates involved in major nuclear functions is fully excluded . Based on this conceptual advance, we propose the following hypotheses.…”

Section: The Anc‐inc Model: Functional Nuclear Organization Based On mentioning

confidence: 99%

The Interchromatin Compartment Participates in the Structural and Functional Organization of the Cell Nucleus

et al. 2020

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This article focuses on the role of the interchromatin compartment (IC) in shaping nuclear landscapes. The IC is connected with nuclear pore complexes (NPCs) and harbors splicing speckles and nuclear bodies. It is postulated that the IC provides routes for imported transcription factors to target sites, for export routes of mRNA as ribonucleoproteins toward NPCs, as well as for the intranuclear passage of regulatory RNAs from sites of transcription to remote functional sites (IC hypothesis). IC channels are lined by less-compacted euchromatin, called the perichromatin region (PR). The PR and IC together form the active nuclear compartment (ANC). The ANC is co-aligned with the inactive nuclear compartment (INC), comprising more compacted heterochromatin. It is postulated that the INC is accessible for individual transcription factors, but inaccessible for larger macromolecular aggregates (limited accessibility hypothesis). This functional nuclear organization depends on still unexplored movements of genes and regulatory sequences between the two compartments.

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“…Mechanistically, transcription can be divided into four stages: (1) The formation of the preinitiation complex, (2) transcription initiation, (3) transcription elongation, and (4) transcription termination (Figure 1). A more detailed biological overview of transcription can be found in other recent reviews (Cramer, 2019;Kujirai and Kurumizaka, 2019;Rodríguez-Enríquez et al, 2019;Babokhov et al, 2020).…”

Section: Targeting Transcriptionmentioning

confidence: 99%

Transcription and Translation Inhibitors in Cancer Treatment

et al. 2020

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Transcription and translation are fundamental cellular processes that govern the protein production of cells. These processes are generally up regulated in cancer cells, to maintain the enhanced metabolism and proliferative state of these cells. As such cancerous cells can be susceptible to transcription and translation inhibitors. There are numerous druggable proteins involved in transcription and translation which make lucrative targets for cancer drug development. In addition to proteins, recent years have shown that the "undruggable" transcription factors and RNA molecules can also be targeted to hamper the transcription or translation in cancer. In this review, we summarize the properties and function of the transcription and translation inhibitors that have been tested and developed, focusing on the advances of the last 5 years. To complement this, we also discuss some of the recent advances in targeting oncogenes tightly controlling transcription including transcription factors and KRAS. In addition to natural and synthetic compounds, we review DNA and RNA based approaches to develop cancer drugs. Finally, we conclude with the outlook to the future of the development of transcription and translation inhibitors.

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Local Chromatin Motion and Transcription

Cited by 34 publications

References 76 publications

Transcriptional suppression of ribosomal DNA with phase separation

Transcriptional suppression of ribosomal DNA with phase separation

The Interchromatin Compartment Participates in the Structural and Functional Organization of the Cell Nucleus

Transcription and Translation Inhibitors in Cancer Treatment

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