Transcription Regulators and Membraneless Organelles Challenges to Investigate Them

Sołtys, Katarzyna; Ożyhar, Andrzej

doi:10.3390/ijms222312758

Cited by 6 publications

(4 citation statements)

References 159 publications

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“…It is also important to clarify that the transcription factories represent by themselves well-defined entities, but more insight into three-dimensional chromatin changes associated with the activation of transcription could arise from the deeper knowledge about nuclear structures such as the membrane-less organelle (MLOs) (39). Evidence exists suggesting that nuclear condensate formation could be involved in the regulation of various aspects of gene expression, as numerous transcription factors, such as the steroid receptors, undergo Liquid-Liquid Phase Separation, the process leading to MLOs formation.…”

Section: Chromatin Looping and Distribution Of Genes In Different Ter...mentioning

confidence: 99%

Chromatin looping links gene expression to the assembly of transcription factories (Review)

Perillo,

Migliaccio,

Castoria

2024

Mol Med Rep

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Genes are not randomly dispersed within the nuclear space, instead they occupy precise sites either with respect to the nuclear lamina as well as to each other. This observation stands at the basis of the today well accepted concept of nuclear territories where any chromosome shows reproducible spatial connections with a selection of others in a general picture that meets a functional criterion where genes that answer the same stimuli are grouped in the same sites. In fact, transcription is not visible widely dispersed throughout the nucleus but is gathered in several 'granules', called transcription factories that accommodates ~10 genes concurrently transcribed. This dynamic behavior of chromosomes is allowed by changes in chromatin plasticity that are governed by several classes of proteins that either modify its building or induce post-translational modifications in the protein component of nucleosomes, triggering formation of chromosome loops that modify the location of specific sites along the DNA strand. For example, transcription associated to nuclear receptors benefits of the generation of nuclear ROS that induce nicks following activation of the DNA repair apparatus that enhance helix unfolding and chromosome bridging. In the present review, the role that protocols facing elucidation of chromosome architecture are playing and will play in the near future were highlighted in order to investigate composition of the transcription factories assembled in response of a specific trigger: The estrogen-sensitive transcription was cited but the authors are convinced that the same portrait will be observed with a multitude of (if not all) other stimuli. Contents1. Introduction 2. Chromatin looping and distribution of genes in different territories and transcription factories 3. Experimental strategies to highlight transcriptional looping 4. Conclusions and future perspectives

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Section: Chromatin Looping and Distribution Of Genes In Different Ter...mentioning

confidence: 99%

Chromatin looping links gene expression to the assembly of transcription factories (Review)

Perillo,

Migliaccio,

Castoria

2024

Mol Med Rep

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“…These domains can be considered more relevant when their inhibition/ablation impairs LLPS formation, or redundant if their inhibition can only prevent LLPS in the absence of another domain (56,97). Like GR, the majority of other SRs need IDRs to stabilize the interaction with co-regulators of this process, such as Med-1, p300/CBP, PCAF, and NCOA1 (92,97,102). This fact points to a common, and probably conserved, mechanism of LLPS that is critical for some of SRs functions as transcriptional regulatory molecules.…”

Section: Phase Separation Associated With Other Steroid Receptors (Ar...mentioning

confidence: 99%

Phase-separation: a possible new layer for transcriptional regulation by glucocorticoid receptor

et al. 2023

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Glucocorticoids (GCs) are hormones involved in circadian adaptation and stress response, and it is also noteworthy that these steroidal molecules present potent anti-inflammatory action through GC receptors (GR). Upon ligand-mediated activation, GR translocates to the nucleus, and regulates gene expression related to metabolism, acute-phase response and innate immune response. GR field of research has evolved considerably in the last decades, providing varied mechanisms that contributed to the understanding of transcriptional regulation and also impacted drug design for treating inflammatory diseases. Liquid-liquid phase separation (LLPS) in cellular processes represents a recent topic in biology that conceptualizes membraneless organelles and microenvironments that promote, or inhibit, chemical reactions and interactions of protein or nucleic acids. The formation of these molecular condensates has been implicated in gene expression control, and recent evidence shows that GR and other steroid receptors can nucleate phase separation (PS). Here we briefly review the varied mechanisms of transcriptional control by GR, which are largely studied in the context of inflammation, and further present how PS can be involved in the control of gene expression. Lastly, we consider how the reported advances on LLPS during transcription control, specially for steroid hormone receptors, could impact the different modalities of GR action on gene expression, adding a new plausible molecular event in glucocorticoid signal transduction.

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“…It has been known for a long time that many TFs have a non-homogeneous distribution in the nucleus and form 10.3389/fmed.2022.1019803 foci (or also termed nuclear puncta) at the DNA target site (182)(183)(184)(185)(186). Liquid-liquid phase separation (LLPS), a recently emerged phenomenon, provides a mechanistic explanation to the formation of these biological condensates, which has been detailed in recent reviews (187)(188)(189). LLPS is a thermodynamically driven reversible phenomenon present from bacteria to humans, and also in plants, reported to be involved in many biological processes and diseases (190)(191)(192)(193).…”

Section: Current Research Gapsmentioning

confidence: 99%

The evolution and polymorphism of mono-amino acid repeats in androgen receptor and their regulatory role in health and disease

Mészáros

Ahmed²,

Russo³

et al. 2022

Front. Med.

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Androgen receptor (AR) is a key member of nuclear hormone receptors with the longest intrinsically disordered N-terminal domain (NTD) in its protein family. There are four mono-amino acid repeats (polyQ1, polyQ2, polyG, and polyP) located within its NTD, of which two are polymorphic (polyQ1 and polyG). The length of both polymorphic repeats shows clinically important correlations with disease, especially with cancer and neurodegenerative diseases, as shorter and longer alleles exhibit significant differences in expression, activity and solubility. Importantly, AR has also been shown to undergo condensation in the nucleus by liquid-liquid phase separation, a process highly sensitive to protein solubility and concentration. Nonetheless, in prostate cancer cells, AR variants also partition into transcriptional condensates, which have been shown to alter the expression of target gene products. In this review, we summarize current knowledge on the link between AR repeat polymorphisms and cancer types, including mechanistic explanations and models comprising the relationship between condensate formation, polyQ1 length and transcriptional activity. Moreover, we outline the evolutionary paths of these recently evolved amino acid repeats across mammalian species, and discuss new research directions with potential breakthroughs and controversies in the literature.

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Transcription Regulators and Membraneless Organelles Challenges to Investigate Them

Cited by 6 publications

References 159 publications

Chromatin looping links gene expression to the assembly of transcription factories (Review)

Chromatin looping links gene expression to the assembly of transcription factories (Review)

Phase-separation: a possible new layer for transcriptional regulation by glucocorticoid receptor

The evolution and polymorphism of mono-amino acid repeats in androgen receptor and their regulatory role in health and disease

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