scholarly journals Histone supply: Multitiered regulation ensures chromatin dynamics throughout the cell cycle

2018 ◽  
Vol 218 (1) ◽  
pp. 39-54 ◽  
Author(s):  
Shweta Mendiratta ◽  
Alberto Gatto ◽  
Genevieve Almouzni

As the building blocks of chromatin, histones are central to establish and maintain particular chromatin states associated with given cell fates. Importantly, histones exist as distinct variants whose expression and incorporation into chromatin are tightly regulated during the cell cycle. During S phase, specialized replicative histone variants ensure the bulk of the chromatinization of the duplicating genome. Other non-replicative histone variants deposited throughout the cell cycle at specific loci use pathways uncoupled from DNA synthesis. Here, we review the particular dynamics of expression, cellular transit, assembly, and disassembly of replicative and non-replicative forms of the histone H3. Beyond the role of histone variants in chromatin dynamics, we review our current knowledge concerning their distinct regulation to control their expression at different levels including transcription, posttranscriptional processing, and protein stability. In light of this unique regulation, we highlight situations where perturbations in histone balance may lead to cellular dysfunction and pathologies.

2021 ◽  
Author(s):  
Isabel Cristina Vélez-Bermúdez ◽  
Wolfgang Schmidt

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.


2009 ◽  
Vol 185 (2) ◽  
pp. 193-202 ◽  
Author(s):  
Arne Lindqvist ◽  
Verónica Rodríguez-Bravo ◽  
René H. Medema

The decision to enter mitosis is mediated by a network of proteins that regulate activation of the cyclin B–Cdk1 complex. Within this network, several positive feedback loops can amplify cyclin B–Cdk1 activation to ensure complete commitment to a mitotic state once the decision to enter mitosis has been made. However, evidence is accumulating that several components of the feedback loops are redundant for cyclin B–Cdk1 activation during normal cell division. Nonetheless, defined feedback loops become essential to promote mitotic entry when normal cell cycle progression is perturbed. Recent data has demonstrated that at least three Plk1-dependent feedback loops exist that enhance cyclin B–Cdk1 activation at different levels. In this review, we discuss the role of various feedback loops that regulate cyclin B–Cdk1 activation under different conditions, the timing of their activation, and the possible identity of the elusive trigger that controls mitotic entry in human cells.


2011 ◽  
Vol 72 (1) ◽  
pp. 25-35 ◽  
Author(s):  
Joanna Ślusarczyk ◽  
Andrzej Wierzbicki ◽  
Marcin Przewłoka ◽  
Teresa Tykarska ◽  
Andrzej Jerzmanowski ◽  
...  

As continuation of investigations in to the mechanism of the role of the H1 histone, which is a crucial protein component chromosomes of all eukaryotes, transgenic tobacco plants with different levels of the H1 histone variants were examined. Tobacco has six sequential variants of the H1 histone: two major ones (H1A and H1B), constituting ca. 90% of all H1, and four minor ones (H1C, H1D, H1E and H1F), occurring in very small quantities. The following groups of plants were examined: K - control group with a full set of histone variants; -AB -with the A and B variants removed; -ABCD - with the A, B, C and D variants removed; and -CD - with the C and D variants removed. The analysis of microsporogenesis in those plants, based on preparations squeezed in acetoorcein, revealed the asynchronous course of meiosis in -AB and -ABCD plants, occurrence of chromosomal aberration, and, consequently, the formation of sterile pollen grains (accordingly: 84,4% and 81,4%). In -CD plants, the percentage of aberration and sterile pollen grains was similar to the control material. Electron microscope observations of microsporogenesis showed ultrastructural changes. In -AB and -ABCD plants, a major portion of the pollen grains were degraded. The smallest number of degraded pollen grains, in comparison with the control, was found in the -CD group.


2020 ◽  
Vol 21 (3) ◽  
pp. 709
Author(s):  
Javier Manzano-López ◽  
Fernando Monje-Casas

The Cdc14 phosphatase is a key regulator of mitosis in the budding yeast Saccharomyces cerevisiae. Cdc14 was initially described as playing an essential role in the control of cell cycle progression by promoting mitotic exit on the basis of its capacity to counteract the activity of the cyclin-dependent kinase Cdc28/Cdk1. A compiling body of evidence, however, has later demonstrated that this phosphatase plays other multiple roles in the regulation of mitosis at different cell cycle stages. Here, we summarize our current knowledge about the pivotal role of Cdc14 in cell cycle control, with a special focus in the most recently uncovered functions of the phosphatase.


2020 ◽  
Vol 21 (18) ◽  
pp. 6578
Author(s):  
Crescenzio Francesco Minervini ◽  
Elisa Parciante ◽  
Luciana Impera ◽  
Luisa Anelli ◽  
Antonella Zagaria ◽  
...  

Epitranscriptomics analyze the biochemical modifications borne by RNA and their downstream influence. From this point of view, epitranscriptomics represent a new layer for the control of genetic information and can affect a variety of molecular processes including the cell cycle and the differentiation. In physiological conditions, hematopoiesis is a tightly regulated process that produces differentiated blood cells starting from hematopoietic stem cells. Alteration of this process can occur at different levels in the pathway that leads from the genetic information to the phenotypic manifestation producing malignant hematopoiesis. This review focuses on the role of epitranscriptomic events that are known to be implicated in normal and malignant hematopoiesis, opening a new pathophysiological and therapeutic scenario. Moreover, an evolutionary vision of this mechanism will be provided.


2012 ◽  
Vol 2012 ◽  
pp. 1-13 ◽  
Author(s):  
Lorena Perrone ◽  
Oualid Sbai ◽  
Peter P. Nawroth ◽  
Angelika Bierhaus

Alzheimer's disease (AD) is the most common cause of dementia. Amyloid plaques and neurofibrillary tangles are prominent pathological features of AD. Aging and age-dependent oxidative stress are the major nongenetic risk factors for AD. The beta-amyloid peptide (Aβ), the major component of plaques, and advanced glycation end products (AGEs) are key activators of plaque-associated cellular dysfunction. Aβ and AGEs bind to the receptor for AGEs (RAGE), which transmits the signal from RAGE via redox-sensitive pathways to nuclear factor kappa-B (NF-κB). RAGE-mediated signaling is an important contributor to neurodegeneration in AD. We will summarize the current knowledge and ongoing studies on RAGE function in AD. We will also present evidence for a novel pathway induced by RAGE in AD, which leads to the expression of thioredoxin interacting protein (TXNIP), providing further evidence that pharmacological inhibition of RAGE will promote neuroprotection by blocking neurovascular dysfunction in AD.


Author(s):  
Lorena Zannino ◽  
Claudio Casali ◽  
Stella Siciliani ◽  
Marco Biggiogera

Abstract In the last decades, it has become increasingly clear how the modulation of spatial organization of chromatin over time and through the cell cycle is closely connected to gene function regulation. Different physicochemical stimuli contribute to the realization of specific transcriptional programs and finally to a specific cellular phenotype. In this review, we aim to describe the current knowledge about the dynamics regulating the movements and the interactions of molecules within the nucleus and their impact on gene functions. In particular, taking into account that these forces exert their effect in a nuclear environment characterized by a high concentration of molecules, we will discuss the role of proteins and structures that regulate these movements and transduce physicochemical signals acting on the cell to the nucleus.


Cells ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 2424
Author(s):  
Juliette Ferrand ◽  
Beatrice Rondinelli ◽  
Sophie E. Polo

Chromatin integrity is key for cell homeostasis and for preventing pathological development. Alterations in core chromatin components, histone proteins, recently came into the spotlight through the discovery of their driving role in cancer. Building on these findings, in this review, we discuss how histone variants and their associated chaperones safeguard genome stability and protect against tumorigenesis. Accumulating evidence supports the contribution of histone variants and their chaperones to the maintenance of chromosomal integrity and to various steps of the DNA damage response, including damaged chromatin dynamics, DNA damage repair, and damage-dependent transcription regulation. We present our current knowledge on these topics and review recent advances in deciphering how alterations in histone variant sequence, expression, and deposition into chromatin fuel oncogenic transformation by impacting cell proliferation and cell fate transitions. We also highlight open questions and upcoming challenges in this rapidly growing field.


Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3115
Author(s):  
Vincenzo Alfano ◽  
Mirjam B. Zeisel ◽  
Massimo Levrero ◽  
Francesca Guerrieri

Hepatocellular carcinoma (HCC) represents the fourth leading and fastest rising cause of cancer death (841,000 new cases and 782,000 deaths annually), and hepatitis B (HBV), with 250 million people chronically infected at risk of developing HCC, accounts for >50% of the cases worldwide. Long non-coding RNAs (lncRNAs), untranslated transcripts longer than 200 nucleotides, are implicated in gene regulation at the transcriptional and post-transcriptional levels, exerting their activities both in the nuclear and cytoplasmic compartments. Thanks to high-throughput sequencing techniques, several lncRNAs have been shown to favor the establishment of chronic HBV infection, to change the host transcriptome to establish a pro-carcinogenic environment, and to directly participate in HCC development and progression. In this review, we summarize current knowledge on the role of lncRNAs in HBV infection and HBV-related liver carcinogenesis and discuss the potential of lncRNAs as predictive or diagnostic biomarkers.


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