Chromatin decondensation is accompanied by a transient increase in transcriptional output

Hausnerová, Viola Vaňková; Lanctôt, Christian

doi:10.1111/boc.201600032

Cited by 7 publications

(4 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, closer examination of the image sections revealed that the vast majority of transcriptional spots were found in regions of low DAPI intensity, which leads us to speculate on a possible link between post-mitotic transcriptional spikes and chromatin decondensation. Such a link would be consistent with our recent results that showed that chromatin decondensation induced by changes in extracellular osmolarity in living interphase cells was accompanied by a transient increase in the transcriptional output of a tagged transgene 44 .…”

Section: Discussionsupporting

confidence: 93%

Transcriptional Output Transiently Spikes Upon Mitotic Exit

Hausnerová

Lanctôt

2017

Sci Rep

Self Cite

View full text Add to dashboard Cite

The pulsatile nature of gene activity has recently emerged as a general property of the transcriptional process. It has been shown that the frequency and amplitude of transcriptional bursts can be subjected to extrinsic regulation. Here we have investigated if these parameters were constant throughout the cell cycle using the single molecule RNA FISH technique. We found evidence of transcriptional spikes upon mitotic exit in three different human cell lines. Recording of cell growth prior to hybridization and immuno-RNA FISH analysis revealed that these spikes were short-lived and subsided before completion of cytokinesis. The transient post-mitotic increase in transcriptional output was found to be the result of cells displaying a higher number of active alleles and/or an increased number of nascent transcripts per active allele, indicating that both the burst fraction and the amplitude of individual bursts can be increased upon mitotic exit. Our results further suggest that distinct regulatory mechanisms are at work shortly after mitotic exit and during the rest of interphase. We speculate that transcriptional spikes are associated with chromatin decondensation, a hallmark of post-mitotic cells that might alter the dynamics of transcriptional regulators and effectors.

show abstract

Section: Discussionsupporting

confidence: 93%

Transcriptional Output Transiently Spikes Upon Mitotic Exit

Hausnerová

Lanctôt

2017

Sci Rep

Self Cite

View full text Add to dashboard Cite

show abstract

“…Many studies in recent years have highlighted the importance of chromatin remodeling within the nucleus as crucial regulators of gene expression [ 28 ]. For example, cell geometry-induced actin remodeling has been shown to result in chromatin condensation, which can lead to transcriptional silencing [ 29 ]. Reducing actomyosin contractility using an actin polymerization inhibitor results in the shuttling of histonedeacetylases (HDACs) to the nucleus, which leads to enhanced chromatin condensation [ 15 , 30 ].…”

Section: Discussionmentioning

confidence: 99%

“…Viala et al reported that the condensed chromatin does not affect the initiation of transcription. Chromatin decondensation triggers increased transcription [ 29 ]. These results suggest that mechanical stretching upregulates Tnmd expression via increased chromatin decondensation.…”

Section: Discussionmentioning

confidence: 99%

Stretch-Induced Tenomodulin Expression Promotes Tenocyte Migration via F-Actin and Chromatin Remodeling

Deng

Zhang

et al. 2021

IJMS

View full text Add to dashboard Cite

The mechanosensitive gene tenomodulin (Tnmd) is implicated in tendon maturation and repair. However, the mechanism by which mechanical loading regulates Tnmd’s expression and its role in tenocyte migration is yet to be defined. Here, we show that Tnmd and migration were upregulated in uniaxial cyclic stress-stimulated tenocytes. The knockdown of Tnmd reduced cell migration in the presence and absence of mechanical loading, suggesting that Tnmd is involved in tenocyte migration. Moreover, the treatment of stress-stimulated tenocytes with the actin inhibitor latrunculin (Lat A), histone acetyltransferase inhibitor anacardic acid (ANA), or histone demethylases inhibitor GSK-J4 suppressed Tnmd expression and tenocyte migration. These results show that actin stress fiber formation and chromatin decondensation regulates Tnmd expression, which might then regulate tenocyte migration. Thus, this study proposes the involvement of the actin and chromatin mechanotransduction pathway in the regulation of Tnmd and reveals a novel role of Tnmd in tenocyte migration. The identification of Tnmd function in tenocyte migration provides insight into the molecular mechanisms involved in Tnmd-mediated tendon repair.

show abstract

“…Exit from mitosis corresponds to transcriptional spike at the genes involved in cell growth, but how is the transcriptional activity restarted and how it contributes to reemerging genome structure is not clear. It is possible that transcription inhibition in condensed mitotic chromatin is established at the elongation stage of transcription and not necessarily initiation (Vaňková Hausnerová & Lanctôt, 2017). In this case, RNA Pol II accumulates on genes and is released into productive transcription as soon as chromatin decondenses, thus ensuring the correct temporal transcription of cell growth-related genes.…”

Section: Role Of Transcription In Shaping the Genomementioning

confidence: 99%

Chromatin reorganization, signaling responses and non-coding RNA regulators in homeostasis and senescence

Josipović¹

View full text Add to dashboard Cite

In mammalian cells, a relatively limited fraction of genetic information is utilized in a variety of ways to give rise to distinct cellular phenotypes. Thus, the genotype essentially acts as input for multilayered regulatory networks, which coordinate cellular activities and ultimately shape cell identity and function. Early studies, focusing on individual components of such regulatory networks, have unraveled core principles of cellular functions. Therein, individual, or small groups of genes are regulated by a defined set of locally acting factors. The idea of such individual regulatory units persists, despite new experimental and computational evidence pointing to extensively intertwined "pan-genomic" regulatory networks. In such emerging models, intricate cellular traits originate from numerous interactions, and the mutual dependencies between distinct regulatory units are further governed by such factors as 3D chromatin architecture, noncoding RNA, and even regulatory crosstalk between cells. Therefore, understanding the mechanisms of accurate spatiotemporal regulation of gene expression requires not only elucidating the roles of individual factors at local nodes, but also their contribution to a collective pan-genomic network.In light of such a view, I combined genomics and functional studies in primary human cells to study the regulatory modes of three diverse molecular factors in the context of cellular homeostasis. In Chapter 1, I examine the contribution of active RNA polymerase II (RNA Pol II) in the intricate process of setting up chromatin organization following exit from mitosis. In Chapter 2, I examine the role of HMGB1 as an architectural and RNA-binding factor mediating key events in cells exiting homeostatic cell cycle progression to enter replicative senescence. In Chapter 3, I explore the regulatory potential of two circRNAs, circCAMSAP1 and circRAB3IP, in navigating the regulation of cell cycle progression and inflammation in human cells. Taken together, these three layers of genomic regulation -via RNA Pol II transcription, a dual-function transcription factor, and a pair of circular non-coding RNAs -exemplify the idea of multi-layered regulation of pan-genomic networks inside human cells.

show abstract

Chromatin decondensation is accompanied by a transient increase in transcriptional output

Abstract: The results presented here shed light on the activity of RNA polymerase II during chromatin condensation and decondensation. As such, they point to a new level of transcriptional regulation.

Cited by 7 publications

References 45 publications

Transcriptional Output Transiently Spikes Upon Mitotic Exit

Transcriptional Output Transiently Spikes Upon Mitotic Exit

Stretch-Induced Tenomodulin Expression Promotes Tenocyte Migration via F-Actin and Chromatin Remodeling

Chromatin reorganization, signaling responses and non-coding RNA regulators in homeostasis and senescence

Contact Info

Product

Resources

About