keyword
https://read.qxmd.com/read/38416817/the-molecular-basis-of-cell-memory-in-mammals-the-epigenetic-cycle
#21
REVIEW
Mencía Espinosa-Martínez, María Alcázar-Fabra, David Landeira
Cell memory refers to the capacity of cells to maintain their gene expression program once the initiating environmental signal has ceased. This exceptional feature is key during the formation of mammalian organisms, and it is believed to be in part mediated by epigenetic factors that can endorse cells with the landmarks required to maintain transcriptional programs upon cell duplication. Here, we review current literature analyzing the molecular basis of epigenetic memory in mammals, with a focus on the mechanisms by which transcriptionally repressive chromatin modifications such as methylation of DNA and histone H3 are propagated through mitotic cell divisions...
March 2024: Science Advances
https://read.qxmd.com/read/38394230/the-gene-regulatory-basis-of-bystander-activation-in-cd8-t-cells
#22
JOURNAL ARTICLE
Neva B Watson, Ravi K Patel, Connor Kean, Janelle Veazey, Oyebola O Oyesola, Nathan Laniewski, Jennifer K Grenier, Jocelyn Wang, Cybelle Tabilas, Kristel J Yee Mon, Adrian J McNairn, Seth A Peng, Samantha P Wesnak, Kito Nzingha, Miles P Davenport, Elia D Tait Wojno, Kristin M Scheible, Norah L Smith, Andrew Grimson, Brian D Rudd
CD8+ T cells are classically recognized as adaptive lymphocytes based on their ability to recognize specific foreign antigens and mount memory responses. However, recent studies indicate that some antigen-inexperienced CD8+ T cells can respond to innate cytokines alone in the absence of cognate T cell receptor stimulation, a phenomenon referred to as bystander activation. Here, we demonstrate that neonatal CD8+ T cells undergo a robust and diverse program of bystander activation, which corresponds to enhanced innate-like protection against unrelated pathogens...
February 23, 2024: Science Immunology
https://read.qxmd.com/read/38388540/cbp1-and-cren7-form-chromatin-like-structures-that-ensure-efficient-transcription-of-long-crispr-arrays
#23
JOURNAL ARTICLE
Fabian Blombach, Michal Sýkora, Jo Case, Xu Feng, Diana P Baquero, Thomas Fouqueau, Duy Khanh Phung, Declan Barker, Mart Krupovic, Qunxin She, Finn Werner
CRISPR arrays form the physical memory of CRISPR adaptive immune systems by incorporating foreign DNA as spacers that are often AT-rich and derived from viruses. As promoter elements such as the TATA-box are AT-rich, CRISPR arrays are prone to harbouring cryptic promoters. Sulfolobales harbour extremely long CRISPR arrays spanning several kilobases, a feature that is accompanied by the CRISPR-specific transcription factor Cbp1. Aberrant Cbp1 expression modulates CRISPR array transcription, but the molecular mechanisms underlying this regulation are unknown...
February 22, 2024: Nature Communications
https://read.qxmd.com/read/38383780/wnt-signalling-control-by-kdm5c-during-development-affects-cognition
#24
JOURNAL ARTICLE
Violetta Karwacki-Neisius, Ahram Jang, Engin Cukuroglu, Albert Tai, Alan Jiao, Danilo Predes, Joon Yoon, Emily Brookes, Jiekai Chen, Aimee Iberg, Florian Halbritter, Katrin Õunap, Jozef Gecz, Thorsten M Schlaeger, Shannan Ho Sui, Jonathan Göke, Xi He, Maria K Lehtinen, Scott L Pomeroy, Yang Shi
Although KDM5C is one of the most frequently mutated genes in X-linked intellectual disability1 , the exact mechanisms that lead to cognitive impairment remain unknown. Here we use human patient-derived induced pluripotent stem cells and Kdm5c knockout mice to conduct cellular, transcriptomic, chromatin and behavioural studies. KDM5C is identified as a safeguard to ensure that neurodevelopment occurs at an appropriate timescale, the disruption of which leads to intellectual disability. Specifically, there is a developmental window during which KDM5C directly controls WNT output to regulate the timely transition of primary to intermediate progenitor cells and consequently neurogenesis...
February 21, 2024: Nature
https://read.qxmd.com/read/38378467/an-emerging-paradigm-in-epigenetic-marking-coordination-of-transcription-and-replication
#25
REVIEW
Tyler K Fenstermaker, Svetlana Petruk, Alexander Mazo
DNA replication and RNA transcription both utilize DNA as a template and therefore need to coordinate their activities. The predominant theory in the field is that in order for the replication fork to proceed, transcription machinery has to be evicted from DNA until replication is complete. If that does not occur, these machineries collide, and these collisions elicit various repair mechanisms which require displacement of one of the enzymes, often RNA polymerase, in order for replication to proceed. This model is also at the heart of the epigenetic bookmarking theory, which implies that displacement of RNA polymerase during replication requires gradual re-building of chromatin structure, which guides recruitment of transcriptional proteins and resumption of transcription...
February 20, 2024: Transcription
https://read.qxmd.com/read/38372750/cellular-forgetting-desensitisation-stress-and-ageing-in-signalling-networks-when-do-cells-refuse-to-learn-more
#26
REVIEW
Tamás Veres, Márk Kerestély, Borbála M Kovács, Dávid Keresztes, Klára Schulc, Erik Seitz, Zsolt Vassy, Dániel V Veres, Peter Csermely
Recent findings show that single, non-neuronal cells are also able to learn signalling responses developing cellular memory. In cellular learning nodes of signalling networks strengthen their interactions e.g. by the conformational memory of intrinsically disordered proteins, protein translocation, miRNAs, lncRNAs, chromatin memory and signalling cascades. This can be described by a generalized, unicellular Hebbian learning process, where those signalling connections, which participate in learning, become stronger...
February 19, 2024: Cellular and Molecular Life Sciences: CMLS
https://read.qxmd.com/read/38372373/transcriptional-repression-across-mitosis-mechanisms-and-functions
#27
JOURNAL ARTICLE
A Contreras, C Perea-Resa
Transcription represents a central aspect of gene expression with RNA polymerase machineries (RNA Pol) driving the synthesis of RNA from DNA template molecules. In eukaryotes, a total of three RNA Pol enzymes generate the plethora of RNA species and RNA Pol II is the one transcribing all protein-coding genes. A high number of cis- and trans-acting factors orchestrates RNA Pol II-mediated transcription by influencing the chromatin recruitment, activation, elongation, and/or termination steps. The levels of DNA accessibility, defining open-euchromatin versus close-heterochromatin, delimits RNA Pol II activity as well as the encounter with other factors acting on chromatin such as the DNA replication or DNA repair machineries...
February 19, 2024: Biochemical Society Transactions
https://read.qxmd.com/read/38370415/cytotoxic-cd8-temra-cells-show-loss-of-chromatin-accessibility-at-genes-associated-with-t-cell-activation
#28
JOURNAL ARTICLE
Lehte Türk, Igor Filippov, Christian Arnold, Judith Zaugg, Liina Tserel, Kai Kisand, Pärt Peterson
As humans age, their memory T cell compartment expands due to the lifelong exposure to antigens. This expansion is characterized by terminally differentiated CD8+ T cells (Temra), which possess NK cell-like phenotype and are associated with chronic inflammatory conditions. Temra cells are predominantly driven by the sporadic reactivation of cytomegalovirus (CMV), yet their epigenomic patterns and cellular heterogeneity remain understudied. To address this gap, we correlated their gene expression profiles with chromatin openness and conducted single-cell transcriptome analysis, comparing them to other CD8+ subsets and CMV-responses...
2024: Frontiers in Immunology
https://read.qxmd.com/read/38361032/polycomb-repression-of-hox-genes-involves-spatial-feedback-but-not-domain-compaction-or-phase-transition
#29
JOURNAL ARTICLE
Sedona Eve Murphy, Alistair Nicol Boettiger
Polycomb group proteins have a critical role in silencing transcription during development. It is commonly proposed that Polycomb-dependent changes in genome folding, which compact chromatin, contribute directly to repression by blocking the binding of activating complexes. Recently, it has also been argued that liquid-liquid demixing of Polycomb proteins facilitates this compaction and repression by phase-separating target genes into a membraneless compartment. To test these models, we used Optical Reconstruction of Chromatin Architecture to trace the Hoxa gene cluster, a canonical Polycomb target, in thousands of single cells...
February 15, 2024: Nature Genetics
https://read.qxmd.com/read/38352334/histone-variant-h2be-enhances-chromatin-accessibility-in-neurons-to-promote-synaptic-gene-expression-and-long-term-memory
#30
Emily R Feierman, Sean Louzon, Nicholas A Prescott, Tracy Biaco, Qingzeng Gao, Qi Qiu, Kyuhyun Choi, Katherine C Palozola, Anna J Voss, Shreya Mehta, Camille Quaye, Katherine Lynch, Marc Fuccillo, Hao Wu, Yael David, Erica Korb
Regulation of histones occurs through multiple mechanisms including exchange with histone variants. Unlike canonical histones, variants are replication-independent and therefore accumulate in post-mitotic cells such as neurons. While recent findings link variants to neurological and neuropsychiatric disorders, few are well studied in the context of the brain. H2BE is the single H2B variant found outside germline tissues, yet its expression and effects on chromatin remained unclear. We applied new tools including novel antibodies, biochemical assays, and sequencing approaches to reveal broad H2BE expression in the brain and its role in regulating chromatin structure, neuronal transcription, and mouse behavior...
January 29, 2024: bioRxiv
https://read.qxmd.com/read/38340731/clonally-heritable-gene-expression-imparts-a-layer-of-diversity-within-cell-types
#31
JOURNAL ARTICLE
Jeff E Mold, Martin H Weissman, Michael Ratz, Michael Hagemann-Jensen, Joanna Hård, Carl-Johan Eriksson, Hosein Toosi, Joseph Berghenstråhle, Christoph Ziegenhain, Leonie von Berlin, Marcel Martin, Kim Blom, Jens Lagergren, Joakim Lundeberg, Rickard Sandberg, Jakob Michaëlsson, Jonas Frisén
Cell types can be classified according to shared patterns of transcription. Non-genetic variability among individual cells of the same type has been ascribed to stochastic transcriptional bursting and transient cell states. Using high-coverage single-cell RNA profiling, we asked whether long-term, heritable differences in gene expression can impart diversity within cells of the same type. Studying clonal human lymphocytes and mouse brain cells, we uncovered a vast diversity of heritable gene expression patterns among different clones of cells of the same type in vivo...
February 2, 2024: Cell Systems
https://read.qxmd.com/read/38318533/aging-differentially-alters-the-transcriptome-and-landscape-of-chromatin-accessibility-in-the-male-and-female-mouse-hippocampus
#32
JOURNAL ARTICLE
Jennifer M Achiro, Yang Tao, Fuying Gao, Chia-Ho Lin, Marika Watanabe, Sylvia Neumann, Giovanni Coppola, Douglas L Black, Kelsey C Martin
Aging-related memory impairment and pathological memory disorders such as Alzheimer's disease differ between males and females, and yet little is known about how aging-related changes in the transcriptome and chromatin environment differ between sexes in the hippocampus. To investigate this question, we compared the chromatin accessibility landscape and gene expression/alternative splicing pattern of young adult and aged mouse hippocampus in both males and females using ATAC-seq and RNA-seq. We detected significant aging-dependent changes in the expression of genes involved in immune response and synaptic function and aging-dependent changes in the alternative splicing of myelin sheath genes...
2024: Frontiers in Molecular Neuroscience
https://read.qxmd.com/read/38318384/nuclear-pore-complex-proteins-are-involved-in-centromere-distribution
#33
JOURNAL ARTICLE
Nanami Ito, Takuya Sakamoto, Yuka Oko, Hikaru Sato, Shigeru Hanamata, Yuki Sakamoto, Sachihiro Matsunaga
The subnuclear distribution of centromeres is cooperatively regulated by condensin II and the linker of nucleoskeleton and cytoskeleton (LINC) complex. However, other nuclear membrane structures and nuclear proteins are probably involved in centromere dynamics and distribution. Here, we focused on the nuclear pore complex (NPC), which is known to regulate gene expression, transcription memory, and chromatin structure in addition to transport between the cytoplasm and nucleoplasm. We report here that some nucleoporins (Nups), including Nup85, Nup133, CG1, Nup93b, and NUA, are involved in centromere scattering in Arabidopsis thaliana ...
February 16, 2024: IScience
https://read.qxmd.com/read/38301269/epigenetic-regulation-of-innate-immune-dynamics-during-inflammation
#34
JOURNAL ARTICLE
Blake A Caldwell, Liwu Li
Innate immune cells play essential roles in modulating both immune defense and inflammation by expressing a diverse array of cytokines and inflammatory mediators, phagocytizing pathogens to promote immune clearance, and assisting with the adaptive immune processes through antigen presentation. Rudimentary innate immune "memory" states such as training, tolerance, and exhaustion develop based on the nature, strength, and duration of immune challenge, thereby enabling dynamic transcriptional reprogramming to alter present and future cell behavior...
February 1, 2024: Journal of Leukocyte Biology
https://read.qxmd.com/read/38294217/n6-methyloxyadenine-mediated-detoxification-and-ferroptosis-confer-a-trade-off-between-multi-fungicide-resistance-and-fitness
#35
JOURNAL ARTICLE
Borui Zhang, Zhiwen Wang, Sicong Zhang, Shan Zhong, Ye Sun, Xili Liu
Multi-fungicide resistance (MFR) is a serious environmental problem, which results in the excessive use of fungicides. Fitness penalty, as a common phenomenon in MFR, can partially counteract the issue of resistance due to the weakened vigor of MFR pathogens. Their underlying mechanism and relationship remain unexplained. By Oxford Nanopore Technologies sequencing and dot blot, we found that N6-methyloxyadenine (6mA) modification, the dominate epigenetic marker in Phytophthora capsici , was significantly altered after MFR emerged...
January 31, 2024: MBio
https://read.qxmd.com/read/38260616/disease-associated-astrocyte-epigenetic-memory-promotes-cns-pathology
#36
Hong-Gyun Lee, Joseph M Rone, Zhaorong Li, Camilo Faust Akl, Seung Won Shin, Joon-Hyuk Lee, Lucas E Flausino, Florian Pernin, Chun-Cheih Chao, Kilian L Kleemann, Lena Srun, Tomer Illouz, Federico Giovannoni, Marc Charabati, Liliana M Sanmarco, Jessica E Kenison, Gavin Piester, Stephanie E J Zandee, Jack Antel, Veit Rothhammer, Michael A Wheeler, Alexandre Prat, Iain C Clark, Francisco J Quintana
Astrocytes play important roles in the central nervous system (CNS) physiology and pathology. Indeed, astrocyte subsets defined by specific transcriptional activation states contribute to the pathology of neurologic diseases, including multiple sclerosis (MS) and its pre-clinical model experimental autoimmune encephalomyelitis (EAE) 1-8 . However, little is known about the stability of these disease-associated astrocyte subsets, their regulation, and whether they integrate past stimulation events to respond to subsequent challenges...
January 5, 2024: bioRxiv
https://read.qxmd.com/read/38246143/from-environmental-responses-to-adaptation-the-roles-of-plant-lncrnas
#37
JOURNAL ARTICLE
Soledad Traubenik, Céline Charon, Thomas Blein
As sessile organisms, plants are continuously exposed to heterogeneous and changing environments and constantly need to adapt their growth strategies. They have evolved complex mechanisms to recognize various stress factors, activate appropriate signaling pathways, and respond accordingly by reprogramming the expression of multiple genes at the transcriptional, post-transcriptional, and even epigenome levels to tolerate stressful conditions such as drought, high temperature, nutrient deficiency, and pathogenic interactions...
January 21, 2024: Plant Physiology
https://read.qxmd.com/read/38238608/the-transcriptional-cofactor-tle3-reciprocally-controls-effector-and-central-memory-cd8-t-cell-fates
#38
JOURNAL ARTICLE
Xin Zhao, Wei Hu, Sung Rye Park, Shaoqi Zhu, Shengen Shawn Hu, Chongzhi Zang, Weiqun Peng, Qiang Shan, Hai-Hui Xue
Antigen-experienced CD8+ T cells form effector and central memory T cells (TEM and TCM cells, respectively); however, the mechanism(s) controlling their lineage plasticity remains incompletely understood. Here we show that the transcription cofactor Tle3 critically regulates TEM and TCM cell fates and lineage stability through dynamic redistribution in antigen-responding CD8+ T cell genome. Genetic ablation of Tle3 promoted CD8+ TCM cell formation at the expense of CD8+ TEM cells. Lineage tracing showed that Tle3-deficient CD8+ TEM cells underwent accelerated conversion into CD8+ TCM cells while retaining robust recall capacity...
February 2024: Nature Immunology
https://read.qxmd.com/read/38234938/expression-of-nkx2-2-in-non-ewing-tumors-with-round-cell-morphology
#39
JOURNAL ARTICLE
Saad M Saeed, Usman Hassan, Mudassar Hussain, Sajid Mushtaq, Sheeba Ishtiaq
Background Round cell sarcomas pose diagnostic challenges due to overlapping histopathological features, necessitating precise immunohistochemical markers for accurate categorization. NKX2.2 has emerged as a sensitive diagnostic tool, particularly in Ewing sarcoma. This study extends this understanding to various round-cell sarcomas, shedding light on the potential diagnostic utility of NKX2.2 beyond its established role. The nuanced exploration of NKX2.2 expression aims to enhance diagnostic strategies, prognostic assessments, and therapeutic developments in the landscape of sarcoma research...
December 2023: Curēus
https://read.qxmd.com/read/38228917/the-mediator-kinase-module-enhances-polymerase-activity-to-regulate-transcriptional-memory-after-heat-stress-in-arabidopsis
#40
JOURNAL ARTICLE
Tim Crawford, Lara Siebler, Aleksandra Sulkowska, Bryan Nowack, Li Jiang, Yufeng Pan, Jörn Lämke, Christian Kappel, Isabel Bäurle
Plants are often exposed to recurring adverse environmental conditions in the wild. Acclimation to high temperatures entails transcriptional responses, which prime plants to better withstand subsequent stress events. Heat stress (HS)-induced transcriptional memory results in more efficient re-induction of transcription upon recurrence of heat stress. Here, we identified CDK8 and MED12, two subunits of the kinase module of the transcription co-regulator complex, Mediator, as promoters of heat stress memory and associated histone modifications in Arabidopsis...
January 16, 2024: EMBO Journal
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