Chromatin Organization and Function in Drosophila

Eukaryotic genomes are packaged into high-order chromatin structures organized in discrete territories inside the cell nucleus, which is surrounded by the nuclear envelope acting as a barrier. This chromatin organization is complex and dynamic and, thus, determining the spatial and temporal distribution and folding of chromosomes within the nucleus is critical for understanding the role of chromatin topology in genome function. Primarily focusing on the regulation of gene expression, we review here how the genome of Drosophila melanogaster is organized into the cell nucleus, from small scale histone–DNA interactions to chromosome and lamina interactions in the nuclear space.

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Dissecting the cell to nucleus, perinucleus and cytosol

Scientific Reports ◽

10.1038/srep04923 ◽

2014 ◽

Vol 4 (1) ◽

Cited By ~ 21

Author(s):

Tattym E. Shaiken ◽

Antone R. Opekun

Keyword(s):

Regulation Of Gene Expression ◽

Genome Integrity ◽

Perinuclear Region ◽

Isolation Method ◽

Total Proteins ◽

Isolation Technique ◽

Unknown Composition ◽

And Function ◽

P53 Tumor Suppressor Protein

Abstract Cells have been described under the microscope as organelles containing cytoplasm and the nucleus. However, an unnoted structure exists between the cytoplasm and the nucleoplasm of eukaryotic cells. In addition to the nuclear envelope, there exists a perinuclear region (PNR or perinucleus) with unknown composition and function. Until now, an investigation of the role of the perinucleus has been restricted by the absence of a PNR isolation method. This manuscript describes a perinucleus isolation technique on the basis of its unique compact organization. The perinucleus was found to contain approximately 15 to 18% of the total proteins of the mammalian cell, almost half of the proteins of nuclei. Using four different normal and cancer cell lines, it was shown that the composition of PNR is highly dynamic. Application of the method showed that translocation of the p53 tumor-suppressor protein to the perinucleus in immortalized MEF cells is correlated with the translocation of p53-stabilizing protein, nucleophosmin (B23), to the PNR. Herein, the concept of the perinuclear region is advanced as a formal, identifiable structure. The roles of the perinucleus in maintaining genome integrity, regulation of gene expression and understanding of malignant transformation are discussed.

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SFPQ Rescues F508del-CFTR Expression and Function in Cystic Fibrosis Bronchial Epithelial Cells

10.21203/rs.3.rs-429698/v1 ◽

2021 ◽

Author(s):

Parameet Kumar ◽

Dharmendra Kumar Soni ◽

Chaitali Sen ◽

Mads B Larsen ◽

Krystyna Mazan-Mamczarz ◽

...

Keyword(s):

Cystic Fibrosis ◽

Epithelial Cells ◽

Molecular Mechanisms ◽

Rna Binding ◽

Regulation Of Gene Expression ◽

Lung Epithelial Cells ◽

Regulation Of Expression ◽

Trafficking Defects ◽

And Function

Abstract Cystic Fibrosis (CF) occurs as a result of mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which lead to misfolding, trafficking defects, and impaired function of the CFTR protein. Splicing factor proline/glutamine-rich (SFPQ) is a multifunctional nuclear RNA-binding protein (RBP) implicated in the regulation of gene expression pathways and intracellular trafficking. Here, we investigated the role of SFPQ in the regulation of the expression and function of F508del-CFTR in CF lung epithelial cells. We find that the expression of SFPQ is reduced in F508del-CFTR CF epithelial cells compared to WT-CFTR control cells. Interestingly, the overexpression of SFPQ in CF cells increases the expression as well as rescues the function of F508del-CFTR. Further, comprehensive transcriptome analyses indicate that SFPQ plays a key role in activating the mutant F508del-CFTR by modulating several cellular signaling pathways. This is the first report on the role of SFPQ in the regulation of expression and function of F508del-CFTR in CF lung disease. Our findings provide new insights into SFPQ-mediated molecular mechanisms and point to possible novel epigenetic therapeutic targets for CF and related pulmonary diseases.

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Critical Role of Types 2 and 3 Deiodinases in the Negative Regulation of Gene Expression by T3 in the Mouse Cerebral Cortex

Endocrinology ◽

10.1210/en.2011-1905 ◽

2012 ◽

Vol 153 (6) ◽

pp. 2919-2928 ◽

Cited By ~ 47

Author(s):

Arturo Hernandez ◽

Beatriz Morte ◽

Mónica M. Belinchón ◽

Ainhoa Ceballos ◽

Juan Bernal

Keyword(s):

Gene Expression ◽

Cerebral Cortex ◽

Thyroid Hormone ◽

Critical Role ◽

Regulation Of Gene Expression ◽

Control Of Gene Expression ◽

High Doses ◽

And Function ◽

Type 3

Thyroid hormones regulate brain development and function through the control of gene expression, mediated by binding of T3 to nuclear receptors. Brain T3 concentration is tightly controlled by homeostatic mechanisms regulating transport and metabolism of T4 and T3. We have examined the role of the inactivating enzyme type 3 deiodinase (D3) in the regulation of 43 thyroid hormone-dependent genes in the cerebral cortex of 30-d-old mice. D3 inactivation increased slightly the expression of two of 22 positively regulated genes and significantly decreased the expression of seven of 21 negatively regulated genes. Administration of high doses of T3 led to significant changes in the expression of 12 positive genes and three negative genes in wild-type mice. The response to T3 treatment was enhanced in D3-deficient mice, both in the number of genes and in the amplitude of the response, demonstrating the role of D3 in modulating T3 action. Comparison of the effects on gene expression observed in D3 deficiency with those in hypothyroidism, hyperthyroidism, and type 2 deiodinase (D2) deficiency revealed that the negative genes are more sensitive to D2 and D3 deficiencies than the positive genes. This observation indicates that, in normal physiological conditions, D2 and D3 play critical roles in maintaining local T3 concentrations within a very narrow range. It also suggests that negatively and positively regulated genes do not have the same physiological significance or that their regulation by thyroid hormone obeys different paradigms at the molecular or cellular levels.

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The role of microRNAs in the legume–Rhizobium nitrogen-fixing symbiosis

Journal of Experimental Botany ◽

10.1093/jxb/eraa018 ◽

2020 ◽

Vol 71 (5) ◽

pp. 1668-1680 ◽

Cited By ~ 1

Author(s):

Nhung T Hoang ◽

Katalin Tóth ◽

Gary Stacey

Keyword(s):

Vascular System ◽

Regulation Of Gene Expression ◽

Lotus Japonicus ◽

Nodule Formation ◽

Nitrogen Fixing ◽

Rna Molecules ◽

Physiological Processes ◽

Leaf Tissues ◽

And Function

Abstract Under nitrogen starvation, most legume plants form a nitrogen-fixing symbiosis with Rhizobium bacteria. The bacteria induce the formation of a novel organ called the nodule in which rhizobia reside as intracellular symbionts and convert atmospheric nitrogen into ammonia. During this symbiosis, miRNAs are essential for coordinating the various plant processes required for nodule formation and function. miRNAs are non-coding, endogenous RNA molecules, typically 20–24 nucleotides long, that negatively regulate the expression of their target mRNAs. Some miRNAs can move systemically within plant tissues through the vascular system, which mediates, for example, communication between the stem/leaf tissues and the roots. In this review, we summarize the growing number of miRNAs that function during legume nodulation focusing on two model legumes, Lotus japonicus and Medicago truncatula, and two important legume crops, soybean (Glycine max) and common bean (Phaseolus vulgaris). This regulation impacts a variety of physiological processes including hormone signaling and spatial regulation of gene expression. The role of mobile miRNAs in regulating legume nodule number is also highlighted.

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Micro RNAS as New Players in Control of Hypothalamic Functions

Creative Surgery and Oncology ◽

10.24060/2076-3093-2019-9-2-138-143 ◽

2019 ◽

Vol 9 (2) ◽

pp. 138-143

Author(s):

O. A. Beylerli ◽

I. F. Gareev ◽

A. T. Beylerli

Keyword(s):

Regulation Of Gene Expression ◽

Vital Role ◽

Key Factors ◽

Eukaryotic Genes ◽

Micro Rnas ◽

A Cell ◽

The Central Nervous System ◽

And Function ◽

Post Transcriptional Regulation

Micro RNAs (miRNAs) are short non-coding RNAs (ncRNAs) of ~22 nucleotides in length involved in the post-transcriptional regulation of gene expression. They were discovered over 15 years ago and their functions are becoming clearer. They play an important role in all biological processes. MiRNAs are important modulators of the expression of eukaryotic genes. Focusing on transcripts encoding proteins they impact on the cellular transcriptome thus helping to determine the destiny of a cell. More and more data emerge to indicate an important functional role of miRNAs in the brain development. Since their discovery many miRNAs have been described as key factors in the development and function of the central nervous system. Some play a significant role in the genesis and differentiation of nerve cells (neurons and glial cells). Notably, it has recently been established that miRNAs play a vital role in the mechanisms underpinning the infantile increase of the gonadotropin-releasing hormone (GnRH) production by neurons in the hypothalamus. This phenomenon is necessary for the onset of puberty in mammals. In this review offers our attempt to describe miRNAs as new players in the control of hypothalamic functions, namely the onset of puberty.

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Tidying-up the plant nuclear space: domains, functions, and dynamics

Journal of Experimental Botany ◽

10.1093/jxb/eraa282 ◽

2020 ◽

Vol 71 (17) ◽

pp. 5160-5178

Author(s):

Ana Paula Santos ◽

Valérie Gaudin ◽

Iva Mozgová ◽

Frédéric Pontvianne ◽

Daniel Schubert ◽

...

Keyword(s):

Regulation Of Gene Expression ◽

Nuclear Periphery ◽

Plant Genome ◽

Nuclear Space ◽

Major Question ◽

3D Genome ◽

Technological Advances ◽

Nuclear Domains ◽

Remarkable Progress

Abstract Understanding how the packaging of chromatin in the nucleus is regulated and organized to guide complex cellular and developmental programmes, as well as responses to environmental cues is a major question in biology. Technological advances have allowed remarkable progress within this field over the last years. However, we still know very little about how the 3D genome organization within the cell nucleus contributes to the regulation of gene expression. The nuclear space is compartmentalized in several domains such as the nucleolus, chromocentres, telomeres, protein bodies, and the nuclear periphery without the presence of a membrane around these domains. The role of these domains and their possible impact on nuclear activities is currently under intense investigation. In this review, we discuss new data from research in plants that clarify functional links between the organization of different nuclear domains and plant genome function with an emphasis on the potential of this organization for gene regulation.

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SFPQ rescues F508del-CFTR expression and function in cystic fibrosis bronchial epithelial cells

Scientific Reports ◽

10.1038/s41598-021-96141-w ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Parameet Kumar ◽

Dharmendra Kumar Soni ◽

Chaitali Sen ◽

Mads B. Larsen ◽

Krystyna Mazan-Mamczarz ◽

...

Keyword(s):

Cystic Fibrosis ◽

Epithelial Cells ◽

Molecular Mechanisms ◽

Rna Binding ◽

Regulation Of Gene Expression ◽

Lung Epithelial Cells ◽

Regulation Of Expression ◽

Trafficking Defects ◽

And Function

AbstractCystic fibrosis (CF) occurs as a result of mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which lead to misfolding, trafficking defects, and impaired function of the CFTR protein. Splicing factor proline/glutamine-rich (SFPQ) is a multifunctional nuclear RNA-binding protein (RBP) implicated in the regulation of gene expression pathways and intracellular trafficking. Here, we investigated the role of SFPQ in the regulation of the expression and function of F508del-CFTR in CF lung epithelial cells. We find that the expression of SFPQ is reduced in F508del-CFTR CF epithelial cells compared to WT-CFTR control cells. Interestingly, the overexpression of SFPQ in CF cells increases the expression as well as rescues the function of F508del-CFTR. Further, comprehensive transcriptome analyses indicate that SFPQ plays a key role in activating the mutant F508del-CFTR by modulating several cellular signaling pathways. This is the first report on the role of SFPQ in the regulation of expression and function of F508del-CFTR in CF lung disease. Our findings provide new insights into SFPQ-mediated molecular mechanisms and point to possible novel epigenetic therapeutic targets for CF and related pulmonary diseases.

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Scanning electron microscopic study of collagen fibrillogenesis and extracellular compartmentalization in the chick embryo tendon

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100142669 ◽

1986 ◽

Vol 44 ◽

pp. 208-209

Author(s):

Grace C.H. Yang

Keyword(s):

Chick Embryo ◽

Extracellular Space ◽

Fibroblast Cell ◽

Collagen Fibrils ◽

Electron Microscopic ◽

Voltage Electron ◽

Scanning Electron Microscopic Study ◽

Microscopic Studies ◽

And Function

The size and organization of collagen fibrils in the extracellular matrix is an important determinant of tissue structure and function. The synthesis and deposition of collagen involves multiple steps which begin within the cell and continue in the extracellular space. High-voltage electron microscopic studies of the chick embryo cornea and tendon suggested that the extracellular space is compartmentalized by the fibroblasts for the regulation of collagen fibril, bundle, and tissue specific macroaggregate formation. The purpose of this study is to gather direct evidence regarding the association of the fibroblast cell surface with newly formed collagen fibrils, and to define the role of the fibroblast in the control and the precise positioning of collagen fibrils, bundles, and macroaggregates during chick tendon development.

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Role of the Cilia Membrane in Control of Microtubule Sliding

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s1431927600002683 ◽

1980 ◽

Vol 38 ◽

pp. 612-615

Author(s):

Edna S. Kaneshiro

Keyword(s):

Control Mechanism ◽

Beat Frequency ◽

Surface Membrane ◽

Ciliary Membrane ◽

Ciliary Beating ◽

Ciliary Reversal ◽

Voltage Dependent ◽

Reversal Mechanism ◽

And Function

It is currently believed that ciliary beating results from microtubule sliding which is restricted in regions to cause bending. Cilia beat can be modified to bring about changes in beat frequency, cessation of beat and reversal in beat direction. In ciliated protozoans these modifications which determine swimming behavior have been shown to be related to intracellular (intraciliary) Ca2+ concentrations. The Ca2+ levels are in turn governed by the surface ciliary membrane which exhibits increased Ca2+ conductance (permeability) in response to depolarization. Mutants with altered behaviors have been isolated. Pawn mutants fail to exhibit reversal of the effective stroke of ciliary beat and therefore cannot swim backward. They lack the increased inward Ca2+ current in response to depolarizing stimuli. Both normal and pawn Paramecium made leaky to Ca2+ by Triton extrac¬tion of the surface membrane exhibit backward swimming only in reactivating solutions containing greater than IO-6 M Ca2+ Thus in pawns the ciliary reversal mechanism itself is left operational and only the control mechanism at the membrane is affected. The topographic location of voltage-dependent Ca2+ channels has been identified as a component of the ciliary mem¬brane since the inward Ca2+ conductance response is eliminated by deciliation and the return of the response occurs during cilia regeneration. Since the ciliary membrane has been impli¬cated in the control of Ca2+ levels in the cilium and therefore is the site of at least one kind of control of microtubule sliding, we have focused our attention on understanding the structure and function of the membrane.

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POPDC proteins and cardiac function

Biochemical Society Transactions ◽

10.1042/bst20190249 ◽

2019 ◽

Vol 47 (5) ◽

pp. 1393-1404 ◽

Cited By ~ 4

Author(s):

Thomas Brand

Keyword(s):

Potential Role ◽

Striated Muscle ◽

Short Review ◽

Effector Proteins ◽

Muscle Disease ◽

Disease Genes ◽

Protein Protein Interaction ◽

Interaction Partners ◽

And Function

Abstract The Popeye domain-containing gene family encodes a novel class of cAMP effector proteins in striated muscle tissue. In this short review, we first introduce the protein family and discuss their structure and function with an emphasis on their role in cyclic AMP signalling. Another focus of this review is the recently discovered role of POPDC genes as striated muscle disease genes, which have been associated with cardiac arrhythmia and muscular dystrophy. The pathological phenotypes observed in patients will be compared with phenotypes present in null and knockin mutations in zebrafish and mouse. A number of protein–protein interaction partners have been discovered and the potential role of POPDC proteins to control the subcellular localization and function of these interacting proteins will be discussed. Finally, we outline several areas, where research is urgently needed.

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