The roles of histone variants in fine-tuning chromatin organization and function

The vascular endothelium consists of a single layer of squamous endothelial cells (ECs) lining the inner surface of blood vessels. Nowadays, it is no longer considered as a simple barrier between the blood and vessel wall, but a central hub to control blood flow homeostasis and fulfill tissue metabolic demands by furnishing oxygen and nutrients. The endothelium regulates the proper functioning of vessels and microcirculation, in terms of tone control, blood fluidity, and fine tuning of inflammatory and redox reactions within the vessel wall and in surrounding tissues. This multiplicity of effects is due to the ability of ECs to produce, process, and release key modulators. Among these, gasotransmitters such as nitric oxide (NO) and hydrogen sulfide (H2S) are very active molecules constitutively produced by endotheliocytes for the maintenance and control of vascular physiological functions, while their impairment is responsible for endothelial dysfunction and cardiovascular disorders such as hypertension, atherosclerosis, and impaired wound healing and vascularization due to diabetes, infections, and ischemia. Upregulation of H2S producing enzymes and administration of H2S donors can be considered as innovative therapeutic approaches to improve EC biology and function, to revert endothelial dysfunction or to prevent cardiovascular disease progression. This review will focus on the beneficial autocrine/paracrine properties of H2S on ECs and the state of the art on H2S potentiating drugs and tools.

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Chromatin Enrichment for Proteomics in Plants (ChEP-P) Implicates the Histone Reader ALFIN-LIKE 6 in Jasmonate Signalling

10.21203/rs.3.rs-669473/v1 ◽

2021 ◽

Author(s):

Isabel Cristina Vélez-Bermúdez ◽

Wolfgang Schmidt

Keyword(s):

Histone Variants ◽

Homeodomain Protein ◽

Chromatin Dynamics ◽

Histone 3 ◽

Plant Homeodomain ◽

Associated Proteins ◽

Bona Fide ◽

Covalent Modifications ◽

And Function

Abstract BackgroundCovalent modifications of core histonesgoverndownstream DNA-templated processes such as transcription by altering chromatin structure and function. Previously, we reported that the plant homeodomain protein ALFIN-LIKE6 (AL6), a bona fide histone reader that preferentially binds trimethylated lysin 4 on histone 3 (H3K4me3), is critical for recalibration of cellular phosphate (Pi) homeostasis and root hair elongation under Pi-deficient conditions. ResultsHere, we demonstrate that AL6 is also involved in the response of Arabidopsis seedlings to jasmonic acid (JA) during skotomorphogenesis, possibly by modulating chromatin dynamics that affect the transcriptional regulation of JA-responsivegenes. Dark-grown al6 seedlings showed a compromised reduction in hypocotyl elongation upon exogenously supplied JA, a response that was calibrated by the availability of Pi in the growth medium. A comparison of protein profiles between wild-type and al6 mutant seedlings using a quantitative Chromatin Enrichment for Proteomics (ChEP) approach,that we modified for plant tissue and designated ChEP-P (ChEP in Plants), yielded a comprehensive suite of chromatin-associated proteins and candidates that may be causative for the mutant phenotype. ConclusionsAltered abundance of proteins involved in chromatin organization in al6 seedlings suggests a role of AL6 in coordinating the deposition of histone variants upon perception of internal or environmental stimuli. Our study shows that ChEP-P is well suited to gain holistic insights into chromatin-related processes in plants. Data are available via ProteomeXchange with identifier PXD026541.

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Histone Variants: The Nexus of Developmental Decisions and Epigenetic Memory

Annual Review of Genetics ◽

10.1146/annurev-genet-022620-100039 ◽

2020 ◽

Vol 54 (1) ◽

pp. 121-149 ◽

Cited By ~ 2

Author(s):

Benjamin Loppin ◽

Frédéric Berger

Keyword(s):

Cell Differentiation ◽

Cell Fate ◽

Histone Variants ◽

Epigenetic Memory ◽

The Core ◽

Nucleosome Dynamics ◽

Nucleosome Structure ◽

Core Histones ◽

And Function ◽

The Impact

Nucleosome dynamics and properties are central to all forms of genomic activities. Among the core histones, H3 variants play a pivotal role in modulating nucleosome structure and function. Here, we focus on the impact of H3 variants on various facets of development. The deposition of the replicative H3 variant following DNA replication is essential for the transmission of the epigenomic information encoded in posttranscriptional modifications. Through this process, replicative H3 maintains cell fate while, in contrast, the replacement H3.3 variant opposes cell differentiation during early embryogenesis. In later steps of development, H3.3 and specialized H3 variants are emerging as new, important regulators of terminal cell differentiation, including neurons and gametes. The specific pathways that regulate the dynamics of the deposition of H3.3 are paramount during reprogramming events that drive zygotic activation and the initiation of a new cycle of development.

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Plant Histone HTB (H2B) Variants in Regulating Chromatin Structure and Function

Plants ◽

10.3390/plants9111435 ◽

2020 ◽

Vol 9 (11) ◽

pp. 1435

Author(s):

Janardan Khadka ◽

Anat Pesok ◽

Gideon Grafi

Keyword(s):

Arabidopsis Thaliana ◽

Chromatin Structure ◽

Developmental Stages ◽

Histone Variants ◽

Structure And Function ◽

Core Histone ◽

Histone H2b ◽

Histone Proteins ◽

Genes Encoding ◽

And Function

Besides chemical modification of histone proteins, chromatin dynamics can be modulated by histone variants. Most organisms possess multiple genes encoding for core histone proteins, which are highly similar in amino acid sequence. The Arabidopsis thaliana genome contains 11 genes encoding for histone H2B (HTBs), 13 for H2A (HTAs), 15 for H3 (HTRs), and 8 genes encoding for histone H4 (HFOs). The finding that histone variants may be expressed in specific tissues and/or during specific developmental stages, often displaying specific nuclear localization and involvement in specific nuclear processes suggests that histone variants have evolved to carry out specific functions in regulating chromatin structure and function and might be important for better understanding of growth and development and particularly the response to stress. In this review, we will elaborate on a group of core histone proteins in Arabidopsis, namely histone H2B, summarize existing data, and illuminate the potential function of H2B variants in regulating chromatin structure and function in Arabidopsis thaliana.

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Plasma membrane calcium ATPase regulates bone mass by fine-tuning osteoclast differentiation and survival

The Journal of Cell Biology ◽

10.1083/jcb.201204067 ◽

2012 ◽

Vol 199 (7) ◽

pp. 1145-1158 ◽

Cited By ~ 42

Author(s):

Hyung Joon Kim ◽

Vikram Prasad ◽

Seok-Won Hyung ◽

Zang Hee Lee ◽

Sang-Won Lee ◽

...

Keyword(s):

Plasma Membrane ◽

Bone Mass ◽

Osteoclast Differentiation ◽

Premenopausal Women ◽

Fine Tuning ◽

Bone Homeostasis ◽

Regulatory Loop ◽

And Function

The precise regulation of Ca2+ dynamics is crucial for proper differentiation and function of osteoclasts. Here we show the involvement of plasma membrane Ca2+ ATPase (PMCA) isoforms 1 and 4 in osteoclastogenesis. In immature/undifferentiated cells, PMCAs inhibited receptor activator of NF-κB ligand–induced Ca2+ oscillations and osteoclast differentiation in vitro. Interestingly, nuclear factor of activated T cell c1 (NFATc1) directly stimulated PMCA transcription, whereas the PMCA-mediated Ca2+ efflux prevented NFATc1 activation, forming a negative regulatory loop. PMCA4 also had an anti-osteoclastogenic effect by reducing NO, which facilitates preosteoclast fusion. In addition to their role in immature cells, increased expression of PMCAs in mature osteoclasts prevented osteoclast apoptosis both in vitro and in vivo. Mice heterozygous for PMCA1 or null for PMCA4 showed an osteopenic phenotype with more osteoclasts on bone surface. Furthermore, PMCA4 expression levels correlated with peak bone mass in premenopausal women. Thus, our results suggest that PMCAs play important roles for the regulation of bone homeostasis in both mice and humans by modulating Ca2+ signaling in osteoclasts.

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Supramolecular DNA nanotechnology

Pure and Applied Chemistry ◽

10.1351/pac-con-09-08-13 ◽

2009 ◽

Vol 81 (12) ◽

pp. 2157-2181 ◽

Cited By ~ 11

Author(s):

Faisal A. Aldaye ◽

Hanadi F. Sleiman

Keyword(s):

Molecular Recognition ◽

Base Pair ◽

Deoxyribonucleic Acid ◽

Materials Science ◽

Dna Nanotechnology ◽

Structure And Function ◽

Fine Tuning ◽

Functional Potential ◽

And Function ◽

Main Material

Nature uses deoxyribonucleic acid (DNA) as the main material for the storage and transmission of life’s blueprint. Today, DNA is being used as a “smart” material to help solve a number of long-standing issues facing researchers in materials science and nanotechnology. In DNA nanotechnology, DNA’s powerful base-pair molecular recognition criteria are utilized to control the final structure and function of the material being generated. A sub-area of research that our group has recently termed “supramolecular DNA nanotechnology” is emerging and is extending the limits of this molecule in nanotechnology by further fine-tuning DNA’s structural and functional potential. This review will discuss the fruition and fundamentals of supramolecular DNA nanotechnology, as well as its future as a viable science in a material world.

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Functions of the nuclear envelope and lamina in development and disease

Biochemical Society Transactions ◽

10.1042/bst0361329 ◽

2008 ◽

Vol 36 (6) ◽

pp. 1329-1334 ◽

Cited By ~ 26

Author(s):

Tatiana V. Cohen ◽

Lidia Hernandez ◽

Colin L. Stewart

Keyword(s):

Transcriptional Regulation ◽

Nuclear Envelope ◽

Chromatin Organization ◽

Signalling Pathways ◽

Mechanical Integrity ◽

Inherited Diseases ◽

And Function

Recent findings that some 24 inherited diseases and anomalies are caused by defects in proteins of the NE (nuclear envelope) and lamina have resulted in a fundamental reassessment of the functions of the NE and underlying lamina. Instead of just regarding the NE and lamina as a molecular filtering device, regulating the transfer of macromolecules between the cytoplasm and nucleus, we now envisage the NE/lamina functioning as a key cellular ‘hub’ in integrating critical functions that include chromatin organization, transcriptional regulation, mechanical integrity of the cell and signalling pathways, as well as acting as a key component in the organization and function of the cytoskeleton.

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Neuroimmune Semaphorin 4A in Cancer Angiogenesis and Inflammation: A Promoter or a Suppressor?

International Journal of Molecular Sciences ◽

10.3390/ijms20010124 ◽

2018 ◽

Vol 20 (1) ◽

pp. 124 ◽

Cited By ~ 4

Author(s):

Apoorva Iyer ◽

Svetlana Chapoval

Keyword(s):

Cell Activation ◽

Immune Cell ◽

Fine Tuning ◽

Breast Cancers ◽

Immune Functions ◽

Immune Cell Activation ◽

Important Regulator ◽

And Function ◽

Axon Guidance Molecule ◽

Guidance Molecule

Neuroimmune semaphorin 4A (Sema4A), a member of semaphorin family of transmembrane and secreted proteins, is an important regulator of neuronal and immune functions. In the nervous system, Sema4A primarily regulates the functional activity of neurons serving as an axon guidance molecule. In the immune system, Sema4A regulates immune cell activation and function, instructing a fine tuning of the immune response. Recent studies have shown a dysregulation of Sema4A expression in several types of cancer such as hepatocellular carcinoma, colorectal, and breast cancers. Cancers have been associated with abnormal angiogenesis. The function of Sema4A in angiogenesis and cancer is not defined. Recent studies have demonstrated Sema4A expression and function in endothelial cells. However, the results of these studies are controversial as they report either pro- or anti-angiogenic Sema4A effects depending on the experimental settings. In this mini-review, we discuss these findings as well as our data on Sema4A regulation of inflammation and angiogenesis, which both are important pathologic processes underlining tumorigenesis and tumor metastasis. Understanding the role of Sema4A in those processes may guide the development of improved therapeutic treatments for cancer.

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Pyruvate dehydrogenase complex and nicotinamide nucleotide transhydrogenase constitute an energy-consuming redox circuit

Biochemical Journal ◽

10.1042/bj20141447 ◽

2015 ◽

Vol 467 (2) ◽

pp. 271-280 ◽

Cited By ~ 66

Author(s):

Kelsey H. Fisher-Wellman ◽

Chien-Te Lin ◽

Terence E. Ryan ◽

Lauren R. Reese ◽

Laura A.A. Gilliam ◽

...

Keyword(s):

Energy Expenditure ◽

Pyruvate Dehydrogenase ◽

Pyruvate Dehydrogenase Complex ◽

Negative Energy ◽

Fine Tuning ◽

Metabolic Balance ◽

Cellular Redox ◽

Nicotinamide Nucleotide Transhydrogenase ◽

And Function ◽

Dehydrogenase Complex

Cellular proteins rely on reversible redox reactions to establish and maintain biological structure and function. How redox catabolic (NAD+/NADH) and anabolic (NADP+/NADPH) processes integrate during metabolism to maintain cellular redox homoeostasis, however, is unknown. The present work identifies a continuously cycling mitochondrial membrane potential (ΔΨm)-dependent redox circuit between the pyruvate dehydrogenase complex (PDHC) and nicotinamide nucleotide transhydrogenase (NNT). PDHC is shown to produce H2O2 in relation to reducing pressure within the complex. The H2O2 produced, however, is effectively masked by a continuously cycling redox circuit that links, via glutathione/thioredoxin, to NNT, which catalyses the regeneration of NADPH from NADH at the expense of ΔΨm. The net effect is an automatic fine-tuning of NNT-mediated energy expenditure to metabolic balance at the level of PDHC. In mitochondria, genetic or pharmacological disruptions in the PDHC–NNT redox circuit negate counterbalance changes in energy expenditure. At the whole animal level, mice lacking functional NNT (C57BL/6J) are characterized by lower energy-expenditure rates, consistent with their well-known susceptibility to diet-induced obesity. These findings suggest the integration of redox sensing of metabolic balance with compensatory changes in energy expenditure provides a potential mechanism by which cellular redox homoeostasis is maintained and body weight is defended during periods of positive and negative energy balance.

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The ryanodine receptor provides high throughput Ca2+-release but is precisely regulated by networks of associated proteins: a focus on proteins relevant to phosphorylation

Biochemical Society Transactions ◽

10.1042/bst20140297 ◽

2015 ◽

Vol 43 (3) ◽

pp. 426-433 ◽

Cited By ~ 12

Author(s):

Fiona O'Brien ◽

Elisa Venturi ◽

Rebecca Sitsapesan

Keyword(s):

Spatial Organization ◽

Ryanodine Receptors ◽

Integrated System ◽

Fine Tuning ◽

Control Mechanisms ◽

Fk 506 ◽

High Resolution Structure ◽

Associated Proteins ◽

And Function ◽

Resolution Structure

Once opened, ryanodine receptors (RyR) are efficient pathways for the release of Ca2+ from the endoplasmic/sarcoplasmic reticulum (ER/SR). The precise nature of the Ca2+-release event, however, requires fine-tuning for the specific process and type of cell involved. For example, the spatial organization of RyRs, the luminal [Ca2+] and the influence of soluble regulators that fluctuate under physiological and pathophysiological control mechanisms, all affect the amplitude and duration of RyR Ca2+ fluxes. Various proteins are docked tightly to the huge bulky structure of RyR and there is growing evidence that, together, they provide a sophisticated and integrated system for regulating RyR channel gating. This review focuses on those proteins that are relevant to phosphorylation of RyR channels with particular reference to the cardiac isoform of RyR (RyR2). How phosphorylation of RyR affects channel activity and whether proteins such as the FK-506 binding proteins (FKBP12 and FKBP12.6) are involved, have been highly controversial subjects for more than a decade. But that is expected given the large number of participating proteins, the relevance of phosphorylation in heart failure and inherited arrhythmic diseases, and the frustrations of predicting relationships between structure and function before the advent of a high resolution structure of RyR.

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