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16 pages, 1280 KiB

Open AccessArticle

Effects of Training Status and Exercise Mode on Global Gene Expression in Skeletal Muscle

by Daniel A. Bizjak, Martina Zügel, Gunnar Treff, Kay Winkert, Achim Jerg, Jens Hudemann, Frank C. Mooren, Karsten Krüger, Andreas Nieß and Jürgen M. Steinacker

Int. J. Mol. Sci. 2021, 22(22), 12578; https://doi.org/10.3390/ijms222212578 - 22 Nov 2021

Cited by 5 | Viewed by 4109

Abstract

The aim of this study was to investigate differences in skeletal muscle gene expression of highly trained endurance and strength athletes in comparison to untrained individuals at rest and in response to either an acute bout of endurance or strength exercise. Endurance (ET, [...] Read more.

The aim of this study was to investigate differences in skeletal muscle gene expression of highly trained endurance and strength athletes in comparison to untrained individuals at rest and in response to either an acute bout of endurance or strength exercise. Endurance (ET, n = 8, VO₂max 67 ± 9 mL/kg/min) and strength athletes (ST, n = 8, 5.8 ± 3.0 training years) as well as untrained controls (E-UT and S-UT, each n = 8) performed an acute endurance or strength exercise test. One day before testing (Pre), 30 min (30′Post) and 3 h (180′Post) afterwards, a skeletal muscle biopsy was obtained from the m. vastus lateralis. Skeletal muscle mRNA was isolated and analyzed by Affymetrix-microarray technology. Pathway analyses were performed to evaluate the effects of training status (trained vs. untrained) and exercise mode-specific (ET vs. ST) transcriptional responses. Differences in global skeletal muscle gene expression between trained and untrained were smaller compared to differences in exercise mode. Maximum differences between ET and ST were found between Pre and 180′Post. Pathway analyses showed increased expression of exercise-related genes, such as nuclear transcription factors (NR4A family), metabolism and vascularization (PGC1-α and VEGF-A), and muscle growth/structure (myostatin, IRS1/2 and HIF1-α. The most upregulated genes in response to acute endurance or strength exercise were the NR4A genes (NR4A1, NR4A2, NR4A3). The mode of acute exercise had a significant effect on transcriptional regulation Pre vs. 180′Post. In contrast, the effect of training status on human skeletal muscle gene expression profiles was negligible compared to strength or endurance specialization. The highest variability in gene expression, especially for the NR4A-family, was observed in trained individuals at 180′Post. Assessment of these receptors might be suitable to obtain a deeper understanding of skeletal muscle adaptive processes to develop optimized training strategies. Full article

(This article belongs to the Special Issue Gene Expression and Chromatin Biology 2.0)

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19 pages, 2939 KiB

Open AccessArticle

Yeast Translation Elongation Factor eIF5A Expression Is Regulated by Nutrient Availability through Different Signalling Pathways

by Marina Barba-Aliaga, Carlos Villarroel-Vicente, Alice Stanciu, Alba Corman, María Teresa Martínez-Pastor and Paula Alepuz

Int. J. Mol. Sci. 2021, 22(1), 219; https://doi.org/10.3390/ijms22010219 - 28 Dec 2020

Cited by 11 | Viewed by 3766

Abstract

Translation elongation factor eIF5A binds to ribosomes to promote peptide bonds between problematic amino acids for the reaction like prolines. eIF5A is highly conserved and essential in eukaryotes, which usually contain two similar but differentially expressed paralogue genes. The human eIF5A-1 isoform is [...] Read more.

Translation elongation factor eIF5A binds to ribosomes to promote peptide bonds between problematic amino acids for the reaction like prolines. eIF5A is highly conserved and essential in eukaryotes, which usually contain two similar but differentially expressed paralogue genes. The human eIF5A-1 isoform is abundant and implicated in some cancer types; the eIF5A-2 isoform is absent in most cells but becomes overexpressed in many metastatic cancers. Several reports have connected eIF5A and mitochondria because it co-purifies with the organelle or its inhibition reduces respiration and mitochondrial enzyme levels. However, the mechanisms of eIF5A mitochondrial function, and whether eIF5A expression is regulated by the mitochondrial metabolism, are unknown. We analysed the expression of yeast eIF5A isoforms Tif51A and Tif51B under several metabolic conditions and in mutants. The depletion of Tif51A, but not Tif51B, compromised yeast growth under respiration and reduced oxygen consumption. Tif51A expression followed dual positive regulation: by high glucose through TORC1 signalling, like other translation factors, to promote growth and by low glucose or non-fermentative carbon sources through Snf1 and heme-dependent transcription factor Hap1 to promote respiration. Upon iron depletion, Tif51A was down-regulated and Tif51B up-regulated. Both were Hap1-dependent. Our results demonstrate eIF5A expression regulation by cellular metabolic status. Full article

(This article belongs to the Special Issue Gene Expression and Chromatin Biology)

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18 pages, 2260 KiB

Open AccessArticle

In Vivo Validation of Alternative FDXR Transcripts in Human Blood in Response to Ionizing Radiation

by Lourdes Cruz-Garcia, Grainne O’Brien, Botond Sipos, Simon Mayes, Aleš Tichý, Igor Sirák, Marie Davídková, Markéta Marková, Daniel J. Turner and Christophe Badie

Int. J. Mol. Sci. 2020, 21(21), 7851; https://doi.org/10.3390/ijms21217851 - 23 Oct 2020

Cited by 28 | Viewed by 3814

Abstract

Following cell stress such as ionising radiation (IR) exposure, multiple cellular pathways are activated. We recently demonstrated that ferredoxin reductase (FDXR) has a remarkable IR-induced transcriptional responsiveness in blood. Here, we provided a first comprehensive FDXR variant profile following DNA damage. First, specific [...] Read more.

Following cell stress such as ionising radiation (IR) exposure, multiple cellular pathways are activated. We recently demonstrated that ferredoxin reductase (FDXR) has a remarkable IR-induced transcriptional responsiveness in blood. Here, we provided a first comprehensive FDXR variant profile following DNA damage. First, specific quantitative real-time polymerase chain reaction (qPCR) primers were designed to establish dose-responses for eight curated FDXR variants, all up-regulated after IR in a dose-dependent manner. The potential role of gender on the expression of these variants was tested, and neither the variants response to IR nor the background level of expression was profoundly affected; moreover, in vitro induction of inflammation temporarily counteracted IR response early after exposure. Importantly, transcriptional up-regulation of these variants was further confirmed in vivo in blood of radiotherapy patients. Full-length nanopore sequencing was performed to identify other FDXR variants and revealed the high responsiveness of FDXR-201 and FDXR-208. Moreover, FDXR-218 and FDXR-219 showed no detectable endogenous expression, but a clear detection after IR. Overall, we characterised 14 FDXR transcript variants and identified for the first time their response to DNA damage in vivo. Future studies are required to unravel the function of these splicing variants, but they already represent a new class of radiation exposure biomarkers. Full article

(This article belongs to the Special Issue Gene Expression and Chromatin Biology)

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9 pages, 3071 KiB

Open AccessArticle

CpG Site-Specific Regulation of Metallothionein-1 Gene Expression

by Shoko Ogushi, Yuya Yoshida, Tsuyoshi Nakanishi and Tomoki Kimura

Int. J. Mol. Sci. 2020, 21(17), 5946; https://doi.org/10.3390/ijms21175946 - 19 Aug 2020

Cited by 12 | Viewed by 3541

Abstract

Metal-binding inducible proteins called metallothioneins (MTs) protect cells from heavy-metal toxicity. Their transcription is regulated by metal response element (MRE)-binding transcription factor-1 (MTF1), which is strongly recruited to MREs in the MT promoters, in response to Zn and Cd. Mouse Mt1 gene promoter [...] Read more.

Metal-binding inducible proteins called metallothioneins (MTs) protect cells from heavy-metal toxicity. Their transcription is regulated by metal response element (MRE)-binding transcription factor-1 (MTF1), which is strongly recruited to MREs in the MT promoters, in response to Zn and Cd. Mouse Mt1 gene promoter contains 5 MREs (a–e), and MTF1 has the highest affinity to MREd. Epigenetic changes like DNA methylation might affect transcription and, therefore, the cytoprotective function of MT genes. To reveal the CpG site(s) critical for Mt1 transcription, we analyzed the methylation status of CpG dinucleotides in the Mt1 gene promoter through bisulfite sequencing in P1798 mouse lymphosarcoma cells, with high or low MT expression. We found demethylated CpG sites near MREd and MREe, in cells with high expression. Next, we compared Mt1 gene-promoter-driven Lucia luciferase gene expression in unmethylated and methylated reporter vectors. To clarify the effect of complete and partial CpG methylation, we used M.SssI (CG→^5mCG) and HhaI (GCGC→G^5mCGC)-methylated reporter vectors. Point mutation analysis revealed that methylation of a CpG site near MREd and MREe strongly inhibited Mt1 gene expression. Our results suggest that the methylation status of this site is important for the regulation of Mt1 gene expression. Full article

(This article belongs to the Special Issue Gene Expression and Chromatin Biology)

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14 pages, 4501 KiB

Open AccessArticle

Genome-Wide Characterization of GRAS Family and Their Potential Roles in Cold Tolerance of Cucumber (Cucumis sativus L.)

by Xiaohong Lu, Wenqian Liu, Chenggang Xiang, Xiaojun Li, Qing Wang, Tao Wang, Zixi Liu, Jiali Zhang, Lihong Gao and Wenna Zhang

Int. J. Mol. Sci. 2020, 21(11), 3857; https://doi.org/10.3390/ijms21113857 - 29 May 2020

Cited by 34 | Viewed by 4576

Abstract

Cucumber (Cucumis sativus L.) is one of the most important cucurbit vegetables but is often subjected to stress during cultivation. GRAS (gibberellic acid insensitive, repressor of GAI, and scarecrow) genes encode a family of transcriptional factors that regulate plant growth [...] Read more.

Cucumber (Cucumis sativus L.) is one of the most important cucurbit vegetables but is often subjected to stress during cultivation. GRAS (gibberellic acid insensitive, repressor of GAI, and scarecrow) genes encode a family of transcriptional factors that regulate plant growth and development. In the model plant Arabidopsis thaliana, GRAS family genes function in formation of axillary meristem and root radial structure, phytohormone (gibberellin) signal transduction, light signal transduction and abiotic/biological stress. In this study, a gene family was comprehensively analyzed from the aspects of evolutionary tree, gene structure, chromosome location, evolutionary and expression pattern by means of bioinformatics; 37 GRAS gene family members have been screened from cucumber. We reconstructed an evolutionary tree based on multiple sequence alignment of the typical GRAS domain and conserved motif sequences with those of other species (A. thaliana and Solanum lycopersicum). Cucumber GRAS family was divided into 10 groups according to the classification of Arabidopsis and tomato genes. We conclude that tandem and segmental duplication have played important roles in the expansion and evolution of the cucumber GRAS (CsaGRAS) family. Expression patterns of CsaGRAS genes in different tissues and under cold treatment, combined with gene ontology annotation and interaction network analysis, revealed potentially different functions for CsaGRAS genes in response to cold tolerance, with members of the SHR, SCR and DELLA subfamilies likely playing important roles. In conclusion, this study provides valuable information and candidate genes for improving cucumber tolerance to cold stress. Full article

(This article belongs to the Special Issue Gene Expression and Chromatin Biology)

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12 pages, 3183 KiB

Open AccessArticle

A Single Amino Acid Change in Nramp6 from Sedum Alfredii Hance Affects Cadmium Accumulation

by Zhuchou Lu, Shuangshuang Chen, Xiaojiao Han, Jin Zhang, Guirong Qiao, Yugen Jiang, Renying Zhuo and Wenmin Qiu

Int. J. Mol. Sci. 2020, 21(9), 3169; https://doi.org/10.3390/ijms21093169 - 30 Apr 2020

Cited by 14 | Viewed by 3100

Abstract

SaNramp6 in Sedum alfredii encodes a membrane-localized metal transporter. We isolated the SaNramp6h allele from the hyperaccumulating ecotype (HE) of S. alfredii. When this allele was expressed in transgenic yeast and Arabidopsis thaliana, it enhanced their cadmium (Cd) sensitivity by increased [...] Read more.

SaNramp6 in Sedum alfredii encodes a membrane-localized metal transporter. We isolated the SaNramp6h allele from the hyperaccumulating ecotype (HE) of S. alfredii. When this allele was expressed in transgenic yeast and Arabidopsis thaliana, it enhanced their cadmium (Cd) sensitivity by increased Cd transport and accumulation. We isolated another allele, SaNramp6n, from a nonhyperaccumulating ecotype (NHE) of S. alfredii. Amino acid sequence comparisons revealed three amino acid differences between SaNramp6h and SaNramp6n. We investigated the Cd transport activity of the Nramp6 allele, and determined which residues are essential for the transport activity. We conducted structure-function analyses of SaNramp6 based on site-directed mutagenesis and functional assays of the mutants in yeast and Arabidopsis. The three residues that differed between SaNramp6h and SaNramp6n were mutated. Only the L157P mutation of SaNramp6h impaired Cd transport. The other mutations, S218N and T504A, did not affect the transport activity of SaNramp6h, indicating that these residues are not essential for metal selectivity. Transgenic plants overexpressing SaNramp6h^L157P showed altered metal accumulation in shoots and roots. Our results suggest that the conserved site L157 is essential for the high metal transport activity of SaNramp6h. This information may be useful for limiting or increasing Cd transport by other plant natural resistance associated macrophage protein (NRAMP) proteins. Full article

(This article belongs to the Special Issue Gene Expression and Chromatin Biology)

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Review

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22 pages, 1661 KiB

Open AccessReview

Control of Gene Expression via the Yeast CWI Pathway

by Ana Belén Sanz, Raúl García, Mónica Pavón-Vergés, José Manuel Rodríguez-Peña and Javier Arroyo

Int. J. Mol. Sci. 2022, 23(3), 1791; https://doi.org/10.3390/ijms23031791 - 4 Feb 2022

Cited by 28 | Viewed by 6001

Abstract

Living cells exposed to stressful environmental situations can elicit cellular responses that guarantee maximal cell survival. Most of these responses are mediated by mitogen-activated protein kinase (MAPK) cascades, which are highly conserved from yeast to humans. Cell wall damage conditions in the yeast [...] Read more.

Living cells exposed to stressful environmental situations can elicit cellular responses that guarantee maximal cell survival. Most of these responses are mediated by mitogen-activated protein kinase (MAPK) cascades, which are highly conserved from yeast to humans. Cell wall damage conditions in the yeast Saccharomyces cerevisiae elicit rescue mechanisms mainly associated with reprogramming specific transcriptional responses via the cell wall integrity (CWI) pathway. Regulation of gene expression by this pathway is coordinated by the MAPK Slt2/Mpk1, mainly via Rlm1 and, to a lesser extent, through SBF (Swi4/Swi6) transcription factors. In this review, we summarize the molecular mechanisms controlling gene expression upon cell wall stress and the role of chromatin structure in these processes. Some of these mechanisms are also discussed in the context of other stresses governed by different yeast MAPK pathways. Slt2 regulates both transcriptional initiation and elongation by interacting with chromatin at the promoter and coding regions of CWI-responsive genes but using different mechanisms for Rlm1- and SBF-dependent genes. Since MAPK pathways are very well conserved in eukaryotic cells and are essential for controlling cellular physiology, improving our knowledge regarding how they regulate gene expression could impact the future identification of novel targets for therapeutic intervention. Full article

(This article belongs to the Special Issue Gene Expression and Chromatin Biology 2.0)

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18 pages, 674 KiB

Open AccessReview

Histone 3 Lysine 27 Trimethylation Signature in Breast Cancer

by Lidia Borkiewicz

Int. J. Mol. Sci. 2021, 22(23), 12853; https://doi.org/10.3390/ijms222312853 - 27 Nov 2021

Cited by 12 | Viewed by 3914

Abstract

Cancer development and progression rely on complicated genetic and also epigenetic changes which regulate gene expression without altering the DNA sequence. Epigenetic mechanisms such as DNA methylation, histone modifications, and regulation by lncRNAs alter protein expression by either promoting gene transcription or repressing [...] Read more.

Cancer development and progression rely on complicated genetic and also epigenetic changes which regulate gene expression without altering the DNA sequence. Epigenetic mechanisms such as DNA methylation, histone modifications, and regulation by lncRNAs alter protein expression by either promoting gene transcription or repressing it. The presence of so-called chromatin modification marks at various gene promoters and gene bodies is associated with normal cell development but also with tumorigenesis and progression of different types of cancer, including the most frequently diagnosed breast cancer. This review is focused on the significance of one of the abundant post-translational modifications of histone 3- trimethylation of lysine 27 (H3K27me3), which was shown to participate in tumour suppressor genes’ silencing. Unlike other reviews in the field, here the overview of existing evidence linking H3K27me3 status with breast cancer biology and the tumour outcome is presented especially in the context of diverse breast cancer subtypes. Moreover, the potential of agents that target H3K27me3 for the treatment of this complex disease as well as H3K27 methylation in cross-talk with other chromatin modifications and lncRNAs are discussed. Full article

(This article belongs to the Special Issue Gene Expression and Chromatin Biology 2.0)

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20 pages, 2717 KiB

Open AccessReview

Deacetylation of Transcription Factors in Carcinogenesis

by Marta Halasa, Kamila Adamczuk, Grzegorz Adamczuk, Syeda Afshan, Andrzej Stepulak, Marek Cybulski and Anna Wawruszak

Int. J. Mol. Sci. 2021, 22(21), 11810; https://doi.org/10.3390/ijms222111810 - 30 Oct 2021

Cited by 12 | Viewed by 3724

Abstract

Reversible Nε-lysine acetylation/deacetylation is one of the most common post-translational modifications (PTM) of histones and non-histone proteins that is regulated by histone acetyltransferases (HATs) and histone deacetylases (HDACs). This epigenetic process is highly involved in carcinogenesis, affecting histone and non-histone proteins’ properties and [...] Read more.

Reversible Nε-lysine acetylation/deacetylation is one of the most common post-translational modifications (PTM) of histones and non-histone proteins that is regulated by histone acetyltransferases (HATs) and histone deacetylases (HDACs). This epigenetic process is highly involved in carcinogenesis, affecting histone and non-histone proteins’ properties and their biological functions. Some of the transcription factors, including tumor suppressors and oncoproteins, undergo this modification altering different cell signaling pathways. HDACs deacetylate their targets, which leads to either the upregulation or downregulation of proteins involved in the regulation of cell cycle and apoptosis, ultimately influencing tumor growth, invasion, and drug resistance. Therefore, epigenetic modifications are of great clinical importance and may constitute a new therapeutic target in cancer treatment. This review is aimed to present the significance of HDACs in carcinogenesis through their influence on functions of transcription factors, and therefore regulation of different signaling pathways, cancer progression, and metastasis. Full article

(This article belongs to the Special Issue Gene Expression and Chromatin Biology 2.0)

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18 pages, 1552 KiB

Open AccessReview

Epigenetic Control of Infant B Cell Precursor Acute Lymphoblastic Leukemia

by Oriol de Barrios and Maribel Parra

Int. J. Mol. Sci. 2021, 22(6), 3127; https://doi.org/10.3390/ijms22063127 - 18 Mar 2021

Cited by 4 | Viewed by 4520

Abstract

B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is a highly aggressive malignancy, with poorer prognosis in infants than in adults. A genetic signature has been associated with this outcome but, remarkably, leukemogenesis is commonly triggered by genetic alterations of embryonic origin that involve the [...] Read more.

B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is a highly aggressive malignancy, with poorer prognosis in infants than in adults. A genetic signature has been associated with this outcome but, remarkably, leukemogenesis is commonly triggered by genetic alterations of embryonic origin that involve the deregulation of chromatin remodelers. This review considers in depth how the alteration of epigenetic profiles (at DNA and histone levels) induces an aberrant phenotype in B lymphocyte progenitors by modulating the oncogenic drivers and tumor suppressors involved in key cancer hallmarks. DNA methylation patterns have been widely studied in BCP-ALL and their correlation with survival has been established. However, the effect of methylation on histone residues can be very different. For instance, methyltransferase KMT2A gene participates in chromosomal rearrangements with several partners, imposing an altered pattern of methylated H3K4 and H3K79 residues, enhancing oncogene promoter activation, and conferring a worse outcome on affected infants. In parallel, acetylation processes provide an additional layer of epigenetic regulation and can alter the chromatin conformation, enabling the binding of regulatory factors. Therefore, an integrated knowledge of all epigenetic disorders is essential to understand the molecular basis of BCP-ALL and to identify novel entry points that can be exploited to improve therapeutic options and disease prognosis. Full article

(This article belongs to the Special Issue Gene Expression and Chromatin Biology)

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25 pages, 1839 KiB

Open AccessReview

Multifaceted Chromatin Structure and Transcription Changes in Plant Stress Response

by Jin-Hong Kim

Int. J. Mol. Sci. 2021, 22(4), 2013; https://doi.org/10.3390/ijms22042013 - 18 Feb 2021

Cited by 56 | Viewed by 5634

Abstract

Sessile plants are exposed throughout their existence to environmental abiotic and biotic stress factors, such as cold, heat, salinity, drought, dehydration, submergence, waterlogging, and pathogen infection. Chromatin organization affects genome stability, and its dynamics are crucial in plant stress responses. Chromatin dynamics are [...] Read more.

Sessile plants are exposed throughout their existence to environmental abiotic and biotic stress factors, such as cold, heat, salinity, drought, dehydration, submergence, waterlogging, and pathogen infection. Chromatin organization affects genome stability, and its dynamics are crucial in plant stress responses. Chromatin dynamics are epigenetically regulated and are required for stress-induced transcriptional regulation or reprogramming. Epigenetic regulators facilitate the phenotypic plasticity of development and the survival and reproduction of plants in unfavorable environments, and they are highly diversified, including histone and DNA modifiers, histone variants, chromatin remodelers, and regulatory non-coding RNAs. They contribute to chromatin modifications, remodeling and dynamics, and constitute a multilayered and multifaceted circuitry for sophisticated and robust epigenetic regulation of plant stress responses. However, this complicated epigenetic regulatory circuitry creates challenges for elucidating the common or differential roles of chromatin modifications for transcriptional regulation or reprogramming in different plant stress responses. Particularly, interacting chromatin modifications and heritable stress memories are difficult to identify in the aspect of chromatin-based epigenetic regulation of transcriptional reprogramming and memory. Therefore, this review discusses the recent updates from the three perspectives—stress specificity or dependence of transcriptional reprogramming, the interplay of chromatin modifications, and transcriptional stress memory in plants. This helps solidify our knowledge on chromatin-based transcriptional reprogramming for plant stress response and memory. Full article

(This article belongs to the Special Issue Gene Expression and Chromatin Biology)

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19 pages, 1120 KiB

Open AccessReview

Capturing and Understanding the Dynamics and Heterogeneity of Gene Expression in the Living Cell

by Amparo Pascual-Ahuir, Josep Fita-Torró and Markus Proft

Int. J. Mol. Sci. 2020, 21(21), 8278; https://doi.org/10.3390/ijms21218278 - 5 Nov 2020

Cited by 14 | Viewed by 5445

Abstract

The regulation of gene expression is a fundamental process enabling cells to respond to internal and external stimuli or to execute developmental programs. Changes in gene expression are highly dynamic and depend on many intrinsic and extrinsic factors. In this review, we highlight [...] Read more.

The regulation of gene expression is a fundamental process enabling cells to respond to internal and external stimuli or to execute developmental programs. Changes in gene expression are highly dynamic and depend on many intrinsic and extrinsic factors. In this review, we highlight the dynamic nature of transient gene expression changes to better understand cell physiology and development in general. We will start by comparing recent in vivo procedures to capture gene expression in real time. Intrinsic factors modulating gene expression dynamics will then be discussed, focusing on chromatin modifications. Furthermore, we will dissect how cell physiology or age impacts on dynamic gene regulation and especially discuss molecular insights into acquired transcriptional memory. Finally, this review will give an update on the mechanisms of heterogeneous gene expression among genetically identical individual cells. We will mainly focus on state-of-the-art developments in the yeast model but also cover higher eukaryotic systems. Full article

(This article belongs to the Special Issue Gene Expression and Chromatin Biology)

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21 pages, 2332 KiB

Open AccessReview

Sharing Marks: H3K4 Methylation and H2B Ubiquitination as Features of Meiotic Recombination and Transcription

by Joan Serrano-Quílez, Sergi Roig-Soucase and Susana Rodríguez-Navarro

Int. J. Mol. Sci. 2020, 21(12), 4510; https://doi.org/10.3390/ijms21124510 - 25 Jun 2020

Cited by 12 | Viewed by 6850

Abstract

Meiosis is a specialized cell division that gives raise to four haploid gametes from a single diploid cell. During meiosis, homologous recombination is crucial to ensure genetic diversity and guarantee accurate chromosome segregation. Both the formation of programmed meiotic DNA double-strand breaks (DSBs) [...] Read more.

Meiosis is a specialized cell division that gives raise to four haploid gametes from a single diploid cell. During meiosis, homologous recombination is crucial to ensure genetic diversity and guarantee accurate chromosome segregation. Both the formation of programmed meiotic DNA double-strand breaks (DSBs) and their repair using homologous chromosomes are essential and highly regulated pathways. Similar to other processes that take place in the context of chromatin, histone posttranslational modifications (PTMs) constitute one of the major mechanisms to regulate meiotic recombination. In this review, we focus on specific PTMs occurring in histone tails as driving forces of different molecular events, including meiotic recombination and transcription. In particular, we concentrate on the influence of H3K4me3, H2BK123ub, and their corresponding molecular machineries that write, read, and erase these histone marks. The Spp1 subunit within the Complex of Proteins Associated with Set1 (COMPASS) is a critical regulator of H3K4me3-dependent meiotic DSB formation. On the other hand, the PAF1c (RNA polymerase II associated factor 1 complex) drives the ubiquitination of H2BK123 by Rad6-Bre1. We also discuss emerging evidence obtained by cryo-electron microscopy (EM) structure determination that has provided new insights into how the “cross-talk” between these two marks is accomplished. Full article

(This article belongs to the Special Issue Gene Expression and Chromatin Biology)

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