Regulation of gene expression by repression condensates during development

AbstractThere is emerging evidence for transcription condensates in the activation of gene expression1–3. However, there is considerably less information regarding transcriptional repression, despite its pervasive importance in regulating gene expression in development and disease. Here, we explore the role of liquid-liquid phase separation (LLPS) in the organization of the Groucho/TLE (Gro) family of transcriptional corepressors, which interact with a variety of sequence-specific repressors such as Hes/Hairy4. Gro-dependent repressors have been implicated in a variety of developmental processes, including segmentation of the Drosophila embryo and somitogenesis in vertebrates. These repressors bind to specific recognition sequences, but instead of interacting with coactivators (e.g., Mediator) they recruit Gro corepressors5. Gro contains a series of WD40 repeats that are thought to mediate oligomerization6. How putative Hes/Gro oligomers repress transcription has been the subject of numerous studies5, 6. Here we show that Hes/Gro complexes form discrete puncta within nuclei of living Ciona embryos. These puncta rapidly dissolve during the onset of mitosis and reappear in the ensuing cell cycle. Modified Hes/Gro complexes that are unable to bind DNA exhibit the properties of viscous liquid droplets, similar to those underlying the biogenesis of P-granules in C. elegans7 and nucleoli in Xenopus oocytes8. These observations provide vivid evidence for LLPS in the control of gene expression and suggest a simple physical exclusion mechanism for transcriptional repression. WD40 repeats have been implicated in a wide variety of cellular processes in addition to transcriptional repression9. We suggest that protein interactions using WD40 motifs might be a common feature of processes reliant on LLPS.

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Removal of H3K27me3 by JMJ Proteins Controls Plant Development and Environmental Responses in Arabidopsis

Frontiers in Plant Science ◽

10.3389/fpls.2021.687416 ◽

2021 ◽

Vol 12 ◽

Author(s):

Nobutoshi Yamaguchi

Keyword(s):

Gene Expression ◽

Plant Development ◽

Transcriptional Repression ◽

Target Genes ◽

Regulation Of Gene Expression ◽

Histone H3 ◽

Control Of Gene Expression ◽

Precise Control ◽

Repressive Histone Modification ◽

Environmental Responses

Trimethylation of histone H3 lysine 27 (H3K27me3) is a highly conserved repressive histone modification that signifies transcriptional repression in plants and animals. In Arabidopsis thaliana, the demethylation of H3K27 is regulated by a group of JUMONJI DOMAIN-CONTANING PROTEIN (JMJ) genes. Transcription of JMJ genes is spatiotemporally regulated during plant development and in response to the environment. Once JMJ genes are transcribed, recruitment of JMJs to target genes, followed by demethylation of H3K27, is critically important for the precise control of gene expression. JMJs function synergistically and antagonistically with transcription factors and/or other epigenetic regulators on chromatin. This review summarizes the latest advances in our understanding of Arabidopsis H3K27me3 demethylases that provide robust and flexible epigenetic regulation of gene expression to direct appropriate development and environmental responses in plants.

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Sexually dimorphic control of gene expression in sensory neurons regulates decision-making behavior in C. elegans

eLife ◽

10.7554/elife.21166 ◽

2017 ◽

Vol 6 ◽

Cited By ~ 25

Author(s):

Zoë A Hilbert ◽

Dennis H Kim

Keyword(s):

Gene Expression ◽

Decision Making ◽

Sensory Neurons ◽

Regulation Of Gene Expression ◽

Sensory Information ◽

Specific Expression ◽

Control Of Gene Expression ◽

Neuron Pair ◽

C Elegans ◽

Male Specific

Animal behavior is directed by the integration of sensory information from internal states and the environment. Neuroendocrine regulation of diverse behaviors of Caenorhabditis elegans is under the control of the DAF-7/TGF-β ligand that is secreted from sensory neurons. Here, we show that C. elegans males exhibit an altered, male-specific expression pattern of daf-7 in the ASJ sensory neuron pair with the onset of reproductive maturity, which functions to promote male-specific mate-searching behavior. Molecular genetic analysis of the switch-like regulation of daf-7 expression in the ASJ neuron pair reveals a hierarchy of regulation among multiple inputs—sex, age, nutritional status, and microbial environment—which function in the modulation of behavior. Our results suggest that regulation of gene expression in sensory neurons can function in the integration of a wide array of sensory information and facilitate decision-making behaviors in C. elegans.

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Genetic and epigenetic control of gene expression by CRISPR–Cas systems

F1000Research ◽

10.12688/f1000research.11113.1 ◽

2017 ◽

Vol 6 ◽

pp. 747 ◽

Cited By ~ 32

Author(s):

Albert Lo ◽

Lei Qi

Keyword(s):

Gene Expression ◽

Transcriptional Repression ◽

Target Identification ◽

Rapid Development ◽

Regulation Of Gene Expression ◽

Short Review ◽

Control Of Gene Expression ◽

Epigenome Editing ◽

Specific Regulation ◽

Screening Approaches

The discovery and adaption of bacterial clustered regularly interspaced short palindromic repeats (CRISPR)–CRISPR-associated (Cas) systems has revolutionized the way researchers edit genomes. Engineering of catalytically inactivated Cas variants (nuclease-deficient or nuclease-deactivated [dCas]) combined with transcriptional repressors, activators, or epigenetic modifiers enable sequence-specific regulation of gene expression and chromatin state. These CRISPR–Cas-based technologies have contributed to the rapid development of disease models and functional genomics screening approaches, which can facilitate genetic target identification and drug discovery. In this short review, we will cover recent advances of CRISPR–dCas9 systems and their use for transcriptional repression and activation, epigenome editing, and engineered synthetic circuits for complex control of the mammalian genome.

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Compendium of Methods to Uncover RNA-Protein Interactions In Vivo

Methods and Protocols ◽

10.3390/mps4010022 ◽

2021 ◽

Vol 4 (1) ◽

pp. 22

Author(s):

Mrinmoyee Majumder ◽

Viswanathan Palanisamy

Keyword(s):

Gene Expression ◽

Protein Interactions ◽

Rna Binding ◽

Rna Binding Proteins ◽

Expression Patterns ◽

Control Of Gene Expression ◽

Regulatory Pathways ◽

Advantages And Disadvantages ◽

Protein Nucleic Acid

Control of gene expression is critical in shaping the pro-and eukaryotic organisms’ genotype and phenotype. The gene expression regulatory pathways solely rely on protein–protein and protein–nucleic acid interactions, which determine the fate of the nucleic acids. RNA–protein interactions play a significant role in co- and post-transcriptional regulation to control gene expression. RNA-binding proteins (RBPs) are a diverse group of macromolecules that bind to RNA and play an essential role in RNA biology by regulating pre-mRNA processing, maturation, nuclear transport, stability, and translation. Hence, the studies aimed at investigating RNA–protein interactions are essential to advance our knowledge in gene expression patterns associated with health and disease. Here we discuss the long-established and current technologies that are widely used to study RNA–protein interactions in vivo. We also present the advantages and disadvantages of each method discussed in the review.

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Identification of a C/EBP-Rel complex in avian lymphoid cells

Molecular and Cellular Biology ◽

10.1128/mcb.14.10.6635-6646.1994 ◽

1994 ◽

Vol 14 (10) ◽

pp. 6635-6646

Author(s):

J A Diehl ◽

M Hannink

Keyword(s):

Gene Expression ◽

Affinity Chromatography ◽

Protein Interactions ◽

Binding Proteins ◽

Regulation Of Gene Expression ◽

Lymphoid Cells ◽

Cytokine Gene Expression ◽

Protein Protein Interactions ◽

Dna Complex ◽

Dna Affinity Chromatography

Protein-protein interactions between the CCAAT box enhancer-binding proteins (C/EBP) and the Rel family of transcription factors have been implicated in the regulation of cytokine gene expression. We have used sequence-specific DNA affinity chromatography to purify a complex from avian T cells that binds to a consensus C/EBP motif. Our results provide evidence that Rel-related proteins are components of the C/EBP-DNA complex as a result of protein-protein interactions with the C/EBP proteins. A polyclonal antiserum raised against the Rel homology domain of v-Rel and antisera raised against two human RelA-derived peptides specifically induced a supershift of the C/EBP-DNA complex in mobility shift assays using the affinity-purified C/EBP. In addition, several kappa B-binding proteins copurified with the avian C/EBP complex through two rounds of sequence-specific DNA affinity chromatography. The kappa B-binding proteins are distinct from the C/EBP proteins that directly contact DNA containing the C/EBP binding site. The identification of a protein complex that binds specifically to a consensus C/EBP site and contains both C/EBP and Rel family members suggests a novel mechanism for regulation of gene expression by Rel family proteins.

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Genome expression dynamics reveals parasitism regulatory landscape of the root-knot nematode Meloidogyne incognita and a promoter motif associated with effector genes

10.1101/2021.04.02.438169 ◽

2021 ◽

Author(s):

Martine Da Rocha ◽

Caroline Bournaud ◽

Julie Dazeniere ◽

Peter Thorpe ◽

Clement Pellegrin ◽

...

Keyword(s):

Gene Expression ◽

Meloidogyne Incognita ◽

Life Stage ◽

Regulation Of Gene Expression ◽

Root Knot Nematode ◽

Root Knot Nematodes ◽

Control Of Gene Expression ◽

Precise Control ◽

Effector Genes ◽

Spatio Temporal

Root-knot nematodes are the major contributor to the crop losses caused by nematodes. Root-knot nematodes secrete effectors into the plant, derived from two sets of pharyngeal gland cells, to manipulate host physiology and immunity. Successful completion of the life cycle, involving successive molts from egg to adult, covers morphologically and functionally distinct stages and will require precise control of gene expression, including effectors. The details of how root-knot nematodes regulate transcription remain sparse. Here, we report a life stage-specific transcriptome of Meloidogyne incognita. Combined with an available annotated genome, we explore the spatio-temporal regulation of gene expression. We reveal gene expression clusters and predicted functions that accompany the major developmental transitions. Focusing on effectors, we identify a putative cis-regulatory motif associated with expression in the dorsal glands: providing an insight into effector regulation. We combine the presence of this motif with several other criteria to predict a novel set of putative dorsal gland effectors. Finally, we show this motif, and thereby its utility, is broadly conserved across the Meloidogyne genus and termed it Mel-DOG. Taken together, we provide the first genome-wide analysis of spatio-temporal gene expression in a root-knot nematode, and identify a new set of candidate effector genes that will guide future functional analyses.

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Regulatory signals in messenger RNA: determinants of nutrient–gene interaction and metabolic compartmentation

British Journal Of Nutrition ◽

10.1017/s0007114598001378 ◽

1998 ◽

Vol 80 (4) ◽

pp. 307-321

Author(s):

John E. Hesketh ◽

M. Helena Vasconcelos ◽

Giovanna Bermano

Keyword(s):

Gene Expression ◽

Transcriptional Regulation ◽

Mrna Stability ◽

Transcriptional Control ◽

Regulation Of Gene Expression ◽

Untranslated Regions ◽

Nutritional Requirements ◽

Control Of Gene Expression ◽

Metabolic Compartmentation ◽

Post Transcriptional Regulation

Nutrition has marked influences on gene expression and an understanding of the interaction between nutrients and gene expression is important in order to provide a basis for determining the nutritional requirements on an individual basis. The effects of nutrition can be exerted at many stages between transcription of the genetic sequence and production of a functional protein. This review focuses on the role of post-transcriptional control, particularly mRNA stability, translation and localization, in the interactions of nutrients with gene expression. The effects of both macronutrients and micronutrients on regulation of gene expression by post-transcriptional mechanisms are presented and the post-transcriptional regulation of specific genes of nutritional relevance (glucose transporters, transferrin, selenoenzymes, metallothionein, lipoproteins) is described in detail. The function of the regulatory signals in the untranslated regions of the mRNA is highlighted in relation to control of mRNA stability, translation and localization and the importance of these mRNA regions to regulation by nutrients is illustrated by reference to specific examples. The localization of mRNA by signals in the untranslated regions and its function in the spatial organization of protein synthesis is described; the potential of such mechanisms to play a key part in nutrient channelling and metabolic compartmentation is discussed. It is concluded that nutrients can influence gene expression through control of the regulatory signals in these untranslated regions and that the post-transcriptional regulation of gene expression by these mechanisms may influence nutritional requirements. It is emphasized that in studies of nutritional control of gene expression it is important not to focus only on regulation through gene promoters but also to consider the possibility of post-transcriptional control.

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The molecular dynamics of long noncoding RNA control of transcription in PTEN and its pseudogene

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1621490114 ◽

2017 ◽

Vol 114 (37) ◽

pp. 9942-9947 ◽

Cited By ~ 20

Author(s):

Nicholas Lister ◽

Galina Shevchenko ◽

James L. Walshe ◽

Jessica Groen ◽

Per Johnsson ◽

...

Keyword(s):

Gene Expression ◽

Rna Structure ◽

Noncoding Rna ◽

Dna Methyltransferase ◽

Regulation Of Gene Expression ◽

Control Of Gene Expression ◽

Phosphatase And Tensin Homolog ◽

Tensin Homolog ◽

Sequence Components ◽

Antisense Lncrnas

RNA has been found to interact with chromatin and modulate gene transcription. In human cells, little is known about how long noncoding RNAs (lncRNAs) interact with target loci in the context of chromatin. We find here, using the phosphatase and tensin homolog (PTEN) pseudogene as a model system, that antisense lncRNAs interact first with a 5′ UTR-containing promoter-spanning transcript, which is then followed by the recruitment of DNA methyltransferase 3a (DNMT3a), ultimately resulting in the transcriptional and epigenetic control of gene expression. Moreover, we find that the lncRNA and promoter-spanning transcript interaction are based on a combination of structural and sequence components of the antisense lncRNA. These observations suggest, on the basis of this one example, that evolutionary pressures may be placed on RNA structure more so than sequence conservation. Collectively, the observations presented here suggest a much more complex and vibrant RNA regulatory world may be operative in the regulation of gene expression.

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Progressive lengthening of 3′ untranslated regions of mRNAs by alternative polyadenylation during mouse embryonic development

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.0900028106 ◽

2009 ◽

Vol 106 (17) ◽

pp. 7028-7033 ◽

Cited By ~ 356

Author(s):

Zhe Ji ◽

Ju Youn Lee ◽

Zhenhua Pan ◽

Bingjun Jiang ◽

Bin Tian

Keyword(s):

Gene Expression ◽

Embryonic Development ◽

Posttranscriptional Regulation ◽

Regulation Of Gene Expression ◽

Alternative Polyadenylation ◽

Untranslated Regions ◽

C2c12 Myoblast ◽

Control Of Gene Expression ◽

Differentiation And Proliferation

The 3′ untranslated regions (3′ UTRs) of mRNAs containcis-acting elements for posttranscriptional regulation of gene expression. Here, we report that mouse genes tend to express mRNAs with longer 3′ UTRs as embryonic development progresses. This global regulation is controlled by alternative polyadenylation and coordinates with initiation of organogenesis and aspects of embryonic development, including morphogenesis, differentiation, and proliferation. Using myogenesis of C2C12 myoblast cells as a model, we recapitulated this process in vitro and found that 3′ UTR lengthening is likely caused by weakening of mRNA polyadenylation activity. Because alternative 3′ UTR sequences are typically longer and have higher AU content than constitutive ones, our results suggest that lengthening of 3′ UTR can significantly augment posttranscriptional control of gene expression during embryonic development, such as microRNA-mediated regulation.

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