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A MORC-driven transcriptional switch controls Toxoplasma developmental trajectories and sexual commitment.
Farhat DC, Swale C, Dard C, Cannella D, Ortet P, Barakat M, Sindikubwabo F, Belmudes L, De Bock PJ, Couté Y, Bougdour A, Hakimi MA
Toxoplasma gondii has a complex life cycle that is typified by asexual development that takes place in vertebrates, and sexual reproduction, which occurs exclusively in felids and is therefore less studied. The developmental transitions rely on changes in the patterns of gene expression, and recent studies have assi... |
Seviteronel, a Novel CYP17 Lyase Inhibitor and Androgen Receptor Antagonist, Radiosensitizes AR-Positive Triple Negative Breast Cancer Cells
Anna R. Michmerhuizen, Benjamin Chandler, Eric Olsen, Kari Wilder-Romans, Leah Moubadder, Meilan Liu, Andrea M. Pesch, Amanda Zhang, Cassandra Ritter, S. Tanner Ward, Alyssa Santola, Shyam Nyati, James M. Rae, Daniel Hayes, Felix Y. Feng, Daniel Spratt, D
Increased rates of locoregional recurrence (LR) have been observed in triple negative breast cancer (TNBC) despite multimodality therapy, including radiation (RT). Recent data suggest inhibiting the androgen receptor (AR) may be an effective radiosensitizing strategy, and AR is expressed in 15–35% of TNBC tumo... |
Identification and Massively Parallel Characterization of Regulatory Elements Driving Neural Induction
Inoue Fumitaka, Kreimer Anat, Ashuach Tal, Ahituv Nadav, Yosef Nir
Epigenomic regulation and lineage-specific gene expression act in concert to drive cellular differentiation, but the temporal interplay between these processes is largely unknown. Using neural induction from human pluripotent stem cells (hPSCs) as a paradigm, we interrogated these dynamics by performing RNA sequenci... |
Epigenetic remodelling licences adult cholangiocytes for organoid formation and liver regeneration.
Aloia L, McKie MA, Vernaz G, Cordero-Espinoza L, Aleksieva N, van den Ameele J, Antonica F, Font-Cunill B, Raven A, Aiese Cigliano R, Belenguer G, Mort RL, Brand AH, Zernicka-Goetz M, Forbes SJ, Miska EA, Huch M
Following severe or chronic liver injury, adult ductal cells (cholangiocytes) contribute to regeneration by restoring both hepatocytes and cholangiocytes. We recently showed that ductal cells clonally expand as self-renewing liver organoids that retain their differentiation capacity into both hepatocytes and ductal ... |
Epigenetic down-regulation of the HIST1 locus predicts better prognosis in acute myeloid leukemia with NPM1 mutation.
Garciaz S, N'guyen Dasi L, Finetti P, Chevalier C, Vernerey J, Poplineau M, Platet N, Audebert S, Pophillat M, Camoin L, Bertucci F, Calmels B, Récher C, Birnbaum D, Chabannon C, Vey N, Duprez E
BACKGROUND: The epigenetic machinery is frequently altered in acute myeloid leukemia. Focusing on cytogenetically normal (CN) AML, we previously described an abnormal H3K27me3 enrichment covering 70 kb on the HIST1 cluster (6.p22) in CN-AML patient blasts. Here, we further investigate the molecular, functional,... |
Preparation of cfMeDIP-seq libraries for methylome profiling of plasma cell-free DNA.
Shen SY, Burgener JM, Bratman SV, De Carvalho DD
Circulating cell-free DNA (cfDNA) comprises small DNA fragments derived from normal and tumor tissue that are released into the bloodstream. Recently, methylation profiling of cfDNA as a liquid biopsy tool has been gaining prominence due to the presence of tissue-specific markers in cfDNA. We have previously reporte... |
EZH2 as a novel therapeutic target for atrial fibrosis and atrial fibrillation.
Song S, Zhang R, Mo B, Chen L, Liu L, Yu Y, Cao W, Fang G, Wan Y, Gu Y, Wang Y, Li Y, Yu Y, Wang Q
Angiotensin II (Ang-II)-induced fibroblast differentiation plays an important role in the development of atrial fibrosis and atrial fibrillation (AF). Here, we show that the expression of the histone methyltransferase enhancer of zeste homolog 2 (EZH2) is increased in atrial muscle and atrial fibroblasts in patients... |
Clinicopathological evaluation of PD-L1 expression and cytotoxic T-lymphocyte infiltrates across intracranial molecular subgroups of ependymomas: are these tumors potential candidates for immune check-point blockade?
Nambirajan A, Malgulwar PB, Sharma A, Boorgula MT, Doddamani R, Singh M, Suri V, Sarkar C, Sharma MC
Immune check-point blockade (ICB) targeting programmed cell death ligand-1 (PD-L1)/programmed death-1 (PD-1) axis has created paradigm shift in cancer treatment. 'ST-RELA' and 'PF-A' molecular subgroups of ependymomas (EPN) show poor outcomes. We aimed to understand the potential candidature of EPNs for ICB. Suprate... |
The Toxoplasma effector TEEGR promotes parasite persistence by modulating NF-κB signalling via EZH2.
Braun L, Brenier-Pinchart MP, Hammoudi PM, Cannella D, Kieffer-Jaquinod S, Vollaire J, Josserand V, Touquet B, Couté Y, Tardieux I, Bougdour A, Hakimi MA
The protozoan parasite Toxoplasma gondii has co-evolved with its homeothermic hosts (humans included) strategies that drive its quasi-asymptomatic persistence in hosts, hence optimizing the chance of transmission to new hosts. Persistence, which starts with a small subset of parasites that escape host immune killing... |
A TetR-family transcription factor regulates fatty acid metabolism in the archaeal model organism Sulfolobus acidocaldarius.
Wang K, Sybers D, Maklad HR, Lemmens L, Lewyllie C, Zhou X, Schult F, Bräsen C, Siebers B, Valegård K, Lindås AC, Peeters E
Fatty acid metabolism and its regulation are known to play important roles in bacteria and eukaryotes. By contrast, although certain archaea appear to metabolize fatty acids, the regulation of the underlying pathways in these organisms remains unclear. Here, we show that a TetR-family transcriptional regulator (FadR... |
Sensitive tumour detection and classification using plasma cell-free DNA methylomes.
Shen SY, Singhania R, Fehringer G, Chakravarthy A, Roehrl MHA, Chadwick D, Zuzarte PC, Borgida A, Wang TT, Li T, Kis O, Zhao Z, Spreafico A, Medina TDS, Wang Y, Roulois D, Ettayebi I, Chen Z, Chow S, Murphy T, Arruda A, O'Kane GM, Liu J, Mansour M, McPher
The use of liquid biopsies for cancer detection and management is rapidly gaining prominence. Current methods for the detection of circulating tumour DNA involve sequencing somatic mutations using cell-free DNA, but the sensitivity of these methods may be low among patients with early-stage cancer given the limited ... |
RbAp48 Protein Is a Critical Component of GPR158/OCN Signaling and Ameliorates Age-Related Memory Loss.
Kosmidis S, Polyzos A, Harvey L, Youssef M, Denny CA, Dranovsky A, Kandel ER
Precisely deciphering the molecular mechanisms of age-related memory loss is crucial to create appropriate therapeutic interventions. We have previously shown that the histone-binding protein RbAp48/Rbbp4 is a molecular determinant of Age-Related Memory Loss. By exploring how this protein regulates the genomic lands... |
Convergent evolution of complex genomic rearrangements in two fungal meiotic drive elements.
Svedberg J, Hosseini S, Chen J, Vogan AA, Mozgova I, Hennig L, Manitchotpisit P, Abusharekh A, Hammond TM, Lascoux M, Johannesson H
Meiotic drive is widespread in nature. The conflict it generates is expected to be an important motor for evolutionary change and innovation. In this study, we investigated the genomic consequences of two large multi-gene meiotic drive elements, Sk-2 and Sk-3, found in the filamentous ascomycete Neurospora intermedi... |
IFN-γ immune priming of macrophages in vivo induces prolonged STAT1 binding and protection against Cryptococcus neoformans.
Leopold Wager CM, Hole CR, Campuzano A, Castro-Lopez N, Cai H, Caballero Van Dyke MC, Wozniak KL, Wang Y, Wormley FL
Development of vaccines against opportunistic infections is difficult as patients most at risk of developing disease are deficient in aspects of the adaptive immune system. Here, we utilized an experimental immunization strategy to induce innate memory in macrophages in vivo. Unlike current trained immunity models, ... |
Histone deacetylase (HDAC) 1 and 2 complexes regulate both histone acetylation and crotonylation in vivo.
Kelly RDW, Chandru A, Watson PJ, Song Y, Blades M, Robertson NS, Jamieson AG, Schwabe JWR, Cowley SM
Proteomic analysis of histones has shown that they are subject to a superabundance of acylations, which extend far beyond acetylation, to include: crotonylation, propionylation, butyrylation, malonylation, succinylation, β-hydroxybutyrylation and 2-hydroxyisobutyrylation. To date, much of the functional data ha... |
Identification of miR-379/miR-656 (C14MC) cluster downregulation and associated epigenetic and transcription regulatory mechanism in oligodendrogliomas.
Kumar A, Nayak S, Pathak P, Purkait S, Malgulawar PB, Sharma MC, Suri V, Mukhopadhyay A, Suri A, Sarkar C
INTRODUCTION: Although role of individual microRNAs (miRNAs) in the pathogenesis of gliomas has been well studied, their role as a clustered remains unexplored in gliomas. METHODS: In this study, we performed the expression analysis of miR-379/miR-656 miRNA-cluster (C14MC) in oligodendrogliomas (ODGs) and also inves... |
Epigenetic regulation of brain region-specific microglia clearance activity.
Ayata P, Badimon A, Strasburger HJ, Duff MK, Montgomery SE, Loh YE, Ebert A, Pimenova AA, Ramirez BR, Chan AT, Sullivan JM, Purushothaman I, Scarpa JR, Goate AM, Busslinger M, Shen L, Losic B, Schaefer A
The rapid elimination of dying neurons and nonfunctional synapses in the brain is carried out by microglia, the resident myeloid cells of the brain. Here we show that microglia clearance activity in the adult brain is regionally regulated and depends on the rate of neuronal attrition. Cerebellar, but not striatal or... |
Polycomb Repressive Complex 2 attenuates the very high expression of the Arabidopsis gene NRT2.1.
Bellegarde F, Herbert L, Séré D, Caillieux E, Boucherez J, Fizames C, Roudier F, Gojon A, Martin A
PRC2 is a major regulator of gene expression in eukaryotes. It catalyzes the repressive chromatin mark H3K27me3, which leads to very low expression of target genes. NRT2.1, which encodes a key root nitrate transporter in Arabidopsis, is targeted by H3K27me3, but the function of PRC2 on NRT2.1 remains unclear. Here, ... |
p27 regulates alpha-synuclein expression.
Gallastegui E, Domuro C, Serratosa J, Larrieux A, Sin L, Martinez J, Besson A, Morante-Redolat JM, Orlando S, Aligue R, Fariñas I, Pujol MJ, Bachs O
Alpha-synuclein (α-SYN) is the main component of anomalous protein aggregates (Lewy bodies) that play a crucial role in several neurodegenerative diseases (synucleinopathies) like Parkinson's disease and multiple system atrophy. However, the mechanisms involved in its transcriptional regulation are poorly unde... |
Chromatin Immunoprecipitation Assay in the Hyperthermoacidophilic Crenarchaeon, Sulfolobus acidocaldarius.
Wang K. et al.
Chromatin immunoprecipitation (ChIP) is a powerful method used for identifying genome-wide DNA-protein interactions in vivo. A large number of essential intracellular processes such as DNA replication, transcription regulation, chromatin stability, and others are all dependent on protein interactions with DNA. The D... |
ChIP-Seq analysis identifies p27(Kip1)-target genes involved in cell adhesion and cell signalling in mouse embryonic fibroblasts
Biçer A. et al.
The protein p27Kip1 (p27), a member of the Cip-Kip family of cyclin-dependent kinase inhibitors, is involved in tumorigenesis and a correlation between reduced levels of this protein in human tumours and a worse prognosis has been established. Recent reports revealed that p27 also behaves as a transcriptional regula... |
PDGFR-modulated miR-23b cluster and miR-125a-5p suppress lung tumorigenesis by targeting multiple components of KRAS and NF-kB pathways
Naidu S. et al.
In NSCLC alterations in PDGF receptors are markers of worst prognosis and efficient targeting of these receptors is yet to be achieved. In this study, we explored PDGFR-regulated microRNAs demonstrating that miR-23b cluster and miR-125a-5p are downregulated by increased expression of PDGFR-α or PDGFR-β in... |
Data on novel DNA methylation changes induced by valproic acid in human hepatocytes
Wolters J. et al.
Valproic acid (VPA) is a widely prescribed antiepileptic drug in the world. Despite its pharmacological importance, it may cause liver toxicity and steatosis. However the exact mechanism of the steatosis formation is unknown. The data presented in this DIB publication is used to further investigate the VPA-induced m... |
Nuclear and Mitochondrial DNA Methylation Patterns Induced by Valproic Acid in Human Hepatocytes
Wolters J.E.J. et al.
Valproic acid (VPA) is one of the most widely prescribed antiepileptic drugs in the world. Despite its pharmacological importance, it may cause liver toxicity and steatosis through mitochondrial dysfunction. The aim of this study is to further investigate VPA-induced mechanisms of steatosis by analyzing changes in p... |
Distinguishing States of Arrest: Genome-Wide Descriptions of Cellular Quiescence Using ChIP-Seq and RNA-Seq Analysis.
Srivastava S. et al.
Regenerative potential in adult stem cells is closely associated with the establishment of-and exit from-a temporary state of quiescence. Emerging evidence not only provides a rationale for the link between lineage determination programs and cell cycle regulation but also highlights the understanding of quiescence a... |
High-Resolution Chromatin Immunoprecipitation: ChIP-Sequencing
Diaz R.E. et al.
Chromatin immunoprecipitation (ChIP) coupled with next-generation sequencing (NGS) is widely used for studying the nucleoprotein components that are involved in the various cellular processes required for shaping the bacterial nucleoid. This methodology, termed ChIP-sequencing (ChIP-seq), enables the identification ... |
Epigenome profiling and editing of neocortical progenitor cells during development
Albert M. et al.
The generation of neocortical neurons from neural progenitor cells (NPCs) is primarily controlled by transcription factors binding to DNA in the context of chromatin. To understand the complex layer of regulation that orchestrates different NPC types from the same DNA sequence, epigenome maps with cell type resoluti... |
Plant-Specific Histone Deacetylases HDT1/2 Regulate GIBBERELLIN 2-OXIDASE2 Expression to Control Arabidopsis Root Meristem Cell Number
Li H. et al.
Root growth is modulated by environmental factors and depends on cell production in the root meristem (RM). New cells in the meristem are generated by stem cells and transit-amplifying cells, which together determine RM cell number. Transcription factors and chromatin-remodeling factors have been implicated in regul... |
MAPK-triggered chromatin reprogramming by histone deacetylase in plant innate immunity
Latrasse D. et al.
Background
Microbial-associated molecular patterns activate several MAP kinases, which are major regulators of the innate immune response in Arabidopsis thaliana that induce large-scale changes in gene expression. Here, we determine whether microbial-associated molecular pattern-triggered gene expression involv... |
The Arabidopsis SWI/SNF protein BAF60 mediates seedling growth control by modulating DNA accessibility
Jégu T. et al.
Background
Plant adaptive responses to changing environments involve complex molecular interplays between intrinsic and external signals. Whilst much is known on the signaling components mediating diurnal, light, and temperature controls on plant development, their influence on chromatin-based transcriptional c... |
LRP8-Reelin-Regulated Neuronal Enhancer Signature Underlying Learning and Memory Formation
Telese F. et al.
One of the exceptional properties of the brain is its ability to acquire new knowledge through learning and to store that information through memory. The epigenetic mechanisms linking changes in neuronal transcriptional programs to behavioral plasticity remain largely unknown. Here, we identify the epigenetic signat... |
PPARγ Links BMP2 and TGFβ1 Pathways in Vascular Smooth Muscle Cells, Regulating Cell Proliferation and Glucose Metabolism
Laurent Calvier, Philippe Chouvarine, Ekaterina Legchenko, Nadine Hoffmann, Jonas Geldner, Paul Borchert, Danny Jonigk, Miklos M. Mozes, Georg Hansmann
BMP2 and TGFβ1 are functional antagonists of pathological remodeling in the arteries, heart, and lung; however, the mechanisms in VSMCs, and their disturbance in pulmonary arterial hypertension (PAH), are unclear. We found a pro-proliferative TGFβ1-Stat3-FoxO1 axis in VSMCs, and PPARγ as in... |
sgs1: a neomorphic nac52 allele impairing PTGS through SGS3 down-regulation
Butel N. et al.
Post-transcriptional gene silencing (PTGS) is a defense mechanism that targets invading nucleic acids from endogenous (transposons) or exogenous (pathogens, transgenes) sources. Genetic screens based on the reactivation of silenced transgenes have long been used to identify cellular components and regulators of PTGS... |
Liver receptor homolog-1 (NR5a2) regulates CD95/Fas ligand transcription and associated T-cell effector functions.
Schwaderer J. et al.
CD95/Fas ligand (FasL) is a cell death-promoting member of the tumor necrosis factor family with important functions in the regulation of T-cell homeostasis and cytotoxicity. In T cells, FasL expression is tightly regulated on a transcriptional level involving a complex set of different transcription factors. The or... |
Development of Peptidomimetic Inhibitors of the ERG Gene Fusion Product in Prostate Cancer
Wang W. et al.
Transcription factors play a key role in the development of diverse cancers, and therapeutically targeting them has remained a challenge. In prostate cancer, the gene encoding the transcription factor ERG is recurrently rearranged and plays a critical role in prostate oncogenesis. Here, we identified a series of pep... |
Hoxa9 and Meis1 Cooperatively Induce Addiction to Syk Signaling by Suppressing miR-146a in Acute Myeloid Leukemia
Mohr S. et al.
The transcription factor Meis1 drives myeloid leukemogenesis in the context of Hox gene overexpression but is currently considered undruggable. We therefore investigated whether myeloid progenitor cells transformed by Hoxa9 and Meis1 become addicted to targetable signaling pathways. A comprehensive (phospho)pro... |
Type I interferon-enhanced IL-10 expression in human CD4 T cells is regulated by STAT3, STAT2, and BATF transcription factors
Govender U. et al.
Type I IFN can exert pro- and anti-inflammatory activities in the immune system. Here, we have investigated the mechanism by which IFN-α enhances early expression of the anti-inflammatory cytokine IL-10 in human CD45RA+CD4+ T cells. With the use of transcriptomic and biochemical approaches, we found distinct a... |
H3K23me1 is an evolutionarily conserved histone modification associated with CG DNA methylation in Arabidopsis
Trejo-Arellano M.S. et al.
Amino-terminal tails of histones are targets for diverse post-translational modifications whose combinatorial action may constitute a code that will be read and interpreted by cellular proteins to define particular transcriptional states. Here, we describe monomethylation of histone H3 lysine 23 (H3K23me1) as a hist... |
Applying the INTACT method to purify endosperm nuclei and to generate parental-specific epigenome profiles.
Moreno-Romero J. et al.
The early endosperm tissue of dicot species is very difficult to isolate by manual dissection. This protocol details how to apply the INTACT (isolation of nuclei tagged in specific cell types) system for isolating early endosperm nuclei of Arabidopsis at high purity and how to generate parental-specific epigenome pr... |
Transcriptional Activation of Pericentromeric Satellite Repeats and Disruption of Centromeric Clustering upon Proteasome Inhibition
Natisvili T. et al.
Heterochromatinisation of pericentromeres, which in mice consist of arrays of major satellite repeats, are important for centromere formation and maintenance of genome stability. The dysregulation of this process has been linked to genomic stress and various cancers. Here we show in mice that the proteasome binds to... |
The lncRNA landscape of breast cancer reveals a role for DSCAM-AS1 in breast cancer progression
Niknafs YS et al.
Molecular classification of cancers into subtypes has resulted in an advance in our understanding of tumour biology and treatment response across multiple tumour types. However, to date, cancer profiling has largely focused on protein-coding genes, which comprise <1% of the genome. Here we leverage a compendium o... |
Dynamic Interplay between the Transcriptome and Methylome in Response to Oxidative and Alkylating Stress
Deferme L et al.
In recent years, it has been shown that free radicals not only react directly with DNA but also regulate epigenetic processes such as DNA methylation, which may be relevant within the context of, for example, tumorigenesis. However, how these free radicals impact the epigenome remains unclear. We therefore investiga... |
Parental epigenetic asymmetry of PRC2-mediated histone modifications in the Arabidopsis endosperm
Moreno-Romero J et al.
Parental genomes in the endosperm are marked by differential DNA methylation and are therefore epigenetically distinct. This epigenetic asymmetry is established in the gametes and maintained after fertilization by unknown mechanisms. In this manuscript, we have addressed the key question whether parentally inherited... |
