keyword
https://read.qxmd.com/read/38451083/histone-h2a-variant-h2a-b-is-enriched-in-transcriptionally-active-and-replicating-hsv-1-lytic-chromatin
#1
JOURNAL ARTICLE
Esteban Flores Cortes, Sarah M Saddoris, Arryn K Owens, Rebecca Gibeault, Daniel P Depledge, Luis M Schang
UNLABELLED: Herpes simplex virus 1 (HSV-1) transcription is restricted in latently infected neurons and the genomes are in mostly silenced chromatin, whereas all viral genes are transcribed in lytically infected cells, in which the genomes are dynamically chromatinized. Epigenetic regulation modulates HSV-1 transcription during lytic, latent, and reactivating infections but the precise mechanisms are not fully defined. Nucleosomes are dynamic: they slide, breathe, assemble, and disassemble...
March 7, 2024: Journal of Virology
https://read.qxmd.com/read/38251858/breast-cancer-malignancy-is-governed-by-regulation-of-the-macroh2a2-tm4sf1-axis-the-akt-nf-%C3%AE%C2%BAb-pathway-and-elevated-mmp13-expression
#2
JOURNAL ARTICLE
Yunho Jin, Da-Young Eum, Chaeyoung Lee, Soon Yong Park, Jae Woong Shim, Yoo Jin Choi, Si Ho Choi, Joong-Gook Kim, Kyu Heo, Seong-Joon Park
The histone variant, macroH2A (mH2A) influences gene expression through epigenetic regulation. Tumor suppressive function of mH2A isoforms has been reported in various cancer types, but few studies have investigated the functional role of mH2A2 in breast cancer pathophysiology. This study aimed to determine the significance of mH2A2 in breast cancer development and progression by exploring its downstream regulatory mechanisms. Knockdown of mH2A2 facilitated the migration and invasion of breast cancer cells, whereas its overexpression exhibited the opposite effect...
January 22, 2024: Molecular Carcinogenesis
https://read.qxmd.com/read/38245506/cyb561-promotes-her2-breast-cancer-proliferation-by-inhibiting-h2afy-degradation
#3
JOURNAL ARTICLE
Ting Zhao, Chaomin Wang, Na Zhao, Ge Qiao, Jialei Hua, Donghua Meng, Liming Liu, Benfu Zhong, Miao Liu, Yichao Wang, Changsen Bai, Yueguo Li
Breast cancer (BRCA) has a high incidence and mortality rate among women. Different molecular subtypes of breast cancer have different prognoses and require personalized therapies. It is imperative to find novel therapeutic targets for different molecular subtypes of BRCA. Here, we demonstrated for the first time that Cytochromeb561 (CYB561) is highly expressed in BRCA and correlates with poor prognosis, especially in HER2-positive BRCA. Overexpression of CYB561 could upregulate macroH2A (H2AFY) expression in HER2-positive BRCA cells through inhibition of H2AFY ubiquitination, and high expression of CYB561 in HER2-positive BRCA cells could promote the proliferation and migration of cells...
January 20, 2024: Cell Death Discovery
https://read.qxmd.com/read/38187672/histone-h2a-variant-h2a-b-is-enriched-in-transcriptionally-active-hsv-1-lytic-chromatin
#4
Esteban Flores, Sarah M Saddoris, Arryn K Owens, Rebecca Gibeault, Daniel P Depledge, Luis M Schang
UNLABELLED: Herpes simplex virus 1 (HSV-1) transcription is restricted in latently infected neurons and the genomes are in mostly silenced chromatin, whereas all viral genes are transcribed in lytically infected cells, in which the genomes are dynamically chromatinized. Epigenetic regulation modulates HSV-1 transcription during lytic, latent, and reactivating infections, but the precise mechanisms are not fully defined. Nucleosomes are dynamic; they slide, breathe, assemble and disassemble...
December 22, 2023: bioRxiv
https://read.qxmd.com/read/38139193/addressing-the-binding-mechanism-of-the-meprin-and-traf-c-homology-domain-of-the-speckle-type-poz-protein-using-protein-engineering
#5
JOURNAL ARTICLE
Awa Diop, Paola Pietrangeli, Valeria Pennacchietti, Livia Pagano, Angelo Toto, Mariana Di Felice, Sara Di Matteo, Lucia Marcocci, Francesca Malagrinò, Stefano Gianni
Protein-protein interactions play crucial roles in a wide range of biological processes, including metabolic pathways, cell cycle progression, signal transduction, and the proteasomal system. For PPIs to fulfill their biological functions, they require the specific recognition of a multitude of interacting partners. In many cases, however, protein-protein interaction domains are capable of binding different partners in the intracellular environment, but they require precise regulation of the binding events in order to exert their function properly and avoid misregulation of important molecular pathways...
December 11, 2023: International Journal of Molecular Sciences
https://read.qxmd.com/read/37858472/the-histone-chaperone-anp32b-regulates-chromatin-incorporation-of-the-atypical-human-histone-variant-macroh2a
#6
JOURNAL ARTICLE
Imke K Mandemaker, Evelyn Fessler, David Corujo, Christiane Kotthoff, Andreas Wegerer, Clément Rouillon, Marcus Buschbeck, Lucas T Jae, Francesca Mattiroli, Andreas G Ladurner
All vertebrate genomes encode for three large histone H2A variants that have an additional metabolite-binding globular macrodomain module, macroH2A. MacroH2A variants impact heterochromatin organization and transcription regulation and establish a barrier for cellular reprogramming. However, the mechanisms of how macroH2A is incorporated into chromatin and the identity of any chaperones required for histone deposition remain elusive. Here, we develop a split-GFP-based assay for chromatin incorporation and use it to conduct a genome-wide mutagenesis screen in haploid human cells to identify proteins that regulate macroH2A dynamics...
October 18, 2023: Cell Reports
https://read.qxmd.com/read/37778979/genome-wide-identification-of-mammalian-cell-cycle-invariant-and-mitotic-specific-macroh2a1-domains
#7
JOURNAL ARTICLE
Le Zhang, Bishan Ye, Zeqian Xu, Xinhui Li, Czajkowsky D M, Zhifeng Shao
The histone variant macroH2A has been found to play important regulatory roles in genomic processes, especially in regulating transcriptomes. However, whether macroH2A nucleosomes are retained on mitotic chromosomes to enable maintenance of cell-specific transcriptomes is not known. Here, examining mouse embryonic fibroblast cells (NIH-3T3) with native chromatin immunoprecipitation and sequencing (nChIP-seq), we show that the overwhelming majority (~90%) of macroH2A1 domains identified at the G1/S stage are indeed stably retained on mitotic chromosomes...
September 29, 2023: Bioscience Trends
https://read.qxmd.com/read/37681758/macroh2a-regulates-inflammation-and-chromatin-looping-in-melanoma
#8
JOURNAL ARTICLE
(no author information available yet)
MacroH2A represses melanoma growth by modulating chromatin architecture and inflammation in the stroma.
September 8, 2023: Cancer Discovery
https://read.qxmd.com/read/37605008/macroh2a-restricts-inflammatory-gene-expression-in-melanoma-cancer-associated-fibroblasts-by-coordinating-chromatin-looping
#9
JOURNAL ARTICLE
Dan Filipescu, Saul Carcamo, Aman Agarwal, Navpreet Tung, Étienne Humblin, Matthew S Goldberg, Nikki S Vyas, Kristin G Beaumont, Deniz Demircioglu, Subhasree Sridhar, Flavia G Ghiraldini, Claudia Capparelli, Andrew E Aplin, Hélène Salmon, Robert Sebra, Alice O Kamphorst, Miriam Merad, Dan Hasson, Emily Bernstein
MacroH2A has established tumour suppressive functions in melanoma and other cancers, but an unappreciated role in the tumour microenvironment. Using an autochthonous, immunocompetent mouse model of melanoma, we demonstrate that mice devoid of macroH2A variants exhibit increased tumour burden compared with wild-type counterparts. MacroH2A-deficient tumours accumulate immunosuppressive monocytes and are depleted of functional cytotoxic T cells, characteristics consistent with a compromised anti-tumour response...
September 2023: Nature Cell Biology
https://read.qxmd.com/read/37494452/phosphorylated-nuclear-dicer1-promotes-open-chromatin-state-and-lineage-plasticity-of-at2-tumor-cells-in-lung-adenocarcinomas
#10
JOURNAL ARTICLE
Raisa A Reyes-Castro, Shin-Yu Chen, Jacob Seemann, Samrat T Kundu, Don L Gibbons, Swathi Arur
KRAS/ERK pathway phosphorylates DICER1, causing its nuclear translocation, and phosphomimetic Dicer1 contributes to tumorigenesis in mice. Mechanisms through which phospho-DICER1 regulates tumor progression remain undefined. While DICER1 canonically regulates microRNAs (miRNA) and epithelial-to-mesenchymal transition (EMT), we found that phosphorylated nuclear DICER1 (phospho-nuclear DICER1) promotes late-stage tumor progression in mice with oncogenic Kras , independent of miRNAs and EMT. Instead, we observe that the murine AT2 tumor cells exhibit altered chromatin compaction, and cells from disorganized advanced tumors, but not localized tumors, express gastric genes...
July 28, 2023: Science Advances
https://read.qxmd.com/read/37432970/combinatorial-targeting-of-a-specific-emt-met-network-by-macroh2a-variants-safeguards-mesenchymal-identity
#11
JOURNAL ARTICLE
Dimitrios Valakos, Eleftheria Klagkou, Antonis Kokkalis, Alexandros Polyzos, Fotis L Kyrilis, Aggelos Banos, Giannis Vatsellas, Maria Pliatska, Ethan Ford, Dimitrios J Stravopodis, Dimitris Thanos
Generation of induced pluripotent stem cells from specialized cell types provides an excellent model to study how cells maintain their stability, and how they can change identity, especially in the context of disease. Previous studies have shown that chromatin safeguards cell identity by acting as a barrier to reprogramming. We investigated mechanisms by which the histone macroH2A variants inhibit reprogramming and discovered that they work as gate keepers of the mesenchymal cell state by blocking epithelial transition, a step required for reprogramming of mouse fibroblasts...
2023: PloS One
https://read.qxmd.com/read/37373284/biophysical-characterization-of-the-binding-mechanism-between-the-math-domain-of-spop-and-its-physiological-partners
#12
JOURNAL ARTICLE
Awa Diop, Paola Pietrangeli, Caterina Nardella, Valeria Pennacchietti, Livia Pagano, Angelo Toto, Mariana Di Felice, Sara Di Matteo, Lucia Marcocci, Francesca Malagrinò, Stefano Gianni
SPOP (Speckle-type POZ protein) is an E3 ubiquitin ligase adaptor protein that mediates the ubiquitination of several substrates. Furthermore, SPOP is responsible for the regulation of both degradable and nondegradable polyubiquitination of a number of substrates with diverse biological functions. The recognition of SPOP and its physiological partners is mediated by two protein-protein interaction domains. Among them, the MATH domain recognizes different substrates, and it is critical for orchestrating diverse cellular pathways, being mutated in several human diseases...
June 14, 2023: International Journal of Molecular Sciences
https://read.qxmd.com/read/36823213/macroh2a-histone-variants-modulate-enhancer-activity-to-repress-oncogenic-programs-and-cellular-reprogramming
#13
JOURNAL ARTICLE
Wazim Mohammed Ismail, Amelia Mazzone, Flavia G Ghiraldini, Jagneet Kaur, Manvir Bains, Amik Munankarmy, Monique S Bagwell, Stephanie L Safgren, John Moore-Weiss, Marina Buciuc, Lynzie Shimp, Kelsey A Leach, Luis F Duarte, Chandandeep S Nagi, Saul Carcamo, Chi-Yeh Chung, Dan Hasson, Neda Dadgar, Jian Zhong, Jeong-Heon Lee, Fergus J Couch, Alexander Revzin, Tamas Ordog, Emily Bernstein, Alexandre Gaspar-Maia
Considerable efforts have been made to characterize active enhancer elements, which can be annotated by accessible chromatin and H3 lysine 27 acetylation (H3K27ac). However, apart from poised enhancers that are observed in early stages of development and putative silencers, the functional significance of cis-regulatory elements lacking H3K27ac is poorly understood. Here we show that macroH2A histone variants mark a subset of enhancers in normal and cancer cells, which we coined 'macro-Bound Enhancers', that modulate enhancer activity...
February 23, 2023: Communications Biology
https://read.qxmd.com/read/36459552/macroh2a-impedes-metastatic-growth-by-enforcing-a-discrete-dormancy-program-in-disseminated-cancer-cells
#14
JOURNAL ARTICLE
Dan Sun, Deepak K Singh, Saul Carcamo, Dan Filipescu, Bassem Khalil, Xin Huang, Brett A Miles, William Westra, Karl Christoph Sproll, Dan Hasson, Emily Bernstein, Julio A Aguirre-Ghiso
MacroH2A variants have been linked to inhibition of metastasis through incompletely understood mechanisms. Here, we reveal that solitary dormant disseminated cancer cells (DCCs) display increased levels of macroH2A variants in head and neck squamous cell carcinoma PDX in vivo models and patient samples compared to proliferating primary or metastatic lesions. We demonstrate that dormancy-inducing transforming growth factor-β2 and p38α/β pathways up-regulate macroH2A expression and that macroH2A variant overexpression is sufficient to induce DCC dormancy and suppress metastasis in vivo...
December 2, 2022: Science Advances
https://read.qxmd.com/read/35732123/macroh2as-regulate-enhancer-promoter-contacts-affecting-enhancer-activity-and-sensitivity-to-inflammatory-cytokines
#15
JOURNAL ARTICLE
David Corujo, Roberto Malinverni, Juan Carrillo-Reixach, Oliver Meers, Arce Garcia-Jaraquemada, Marguerite-Marie Le Pannérer, Vanesa Valero, Ainhoa Pérez, Álvaro Del Río-Álvarez, Laura Royo, Beatriz Pérez-González, Helena Raurell, Rafael D Acemel, José M Santos-Pereira, Marta Garrido-Pontnou, José Luis Gómez-Skarmeta, Lorenzo Pasquali, Josep Manyé, Carolina Armengol, Marcus Buschbeck
MacroH2A histone variants have a function in gene regulation that is poorly understood at the molecular level. We report that macroH2A1.2 and macroH2A2 modulate the transcriptional ground state of cancer cells and how they respond to inflammatory cytokines. Removal of macroH2A1.2 and macroH2A2 in hepatoblastoma cells affects the contact frequency of promoters and distal enhancers coinciding with changes in enhancer activity or preceding them in response to the cytokine tumor necrosis factor alpha. Although macroH2As regulate genes in both directions, they globally facilitate the nuclear factor κB (NF-κB)-mediated response...
June 21, 2022: Cell Reports
https://read.qxmd.com/read/35590030/histone-macroh2a1-is-a-stronger-regulator-of-hippocampal-transcription-and-memory-than-macroh2a2-in-mice
#16
JOURNAL ARTICLE
Gurdeep Singh, Gilda Stefanelli, Klotilda Narkaj, Mark A Brimble, Samantha D Creighton, Timothy A B McLean, Meaghan Hall, Krista A Mitchnick, Jacqueline Zakaria, Thanh Phung, Anas Reda, Amanda M Leonetti, Ashley Monks, Lara Ianov, Boyer D Winters, Brandon J Walters, Andrew M Davidoff, Jennifer A Mitchell, Iva B Zovkic
Histone variants H2A.Z and H3.3 are epigenetic regulators of memory, but roles of other variants are not well characterized. macroH2A (mH2A) is a structurally unique histone that contains a globular macrodomain connected to the histone region by an unstructured linker. Here we assessed if mH2A regulates memory and if this role varies for the two mH2A-encoding genes, H2afy (mH2A1) and H2afy2 (mH2A2). We show that fear memory is impaired in mH2A1, but not in mH2A2-deficient mice, whereas both groups were impaired in a non-aversive spatial memory task...
May 19, 2022: Communications Biology
https://read.qxmd.com/read/35570098/histone-renegades-unusual-h2a-histone-variants-in-plants-and-animals
#17
REVIEW
Akihisa Osakabe, Antoine Molaro
H2A variants are histones that carry out specialized nucleosome function during the eukaryote genome packaging. Most genes encoding H2A histone variants arose in the distant past, and have highly conserved domains and structures. Yet, novel H2A variants have continued to arise throughout the radiation of eukaryotes and disturbed the apparent tranquility of nucleosomes. These species-specific H2A variants contributed to the functional diversification of nucleosomes through changes in both their structure and expression patterns...
May 12, 2022: Seminars in Cell & Developmental Biology
https://read.qxmd.com/read/35422391/evolution-structure-and-function-of-divergent-macroh2a1-splice-isoforms
#18
REVIEW
Iva Guberovic, Marina Farkas, David Corujo, Marcus Buschbeck
The replacement of replication-coupled histones with non-canonical histone variants provides chromatin with additional properties and contributes to the plasticity of the epigenome. MacroH2A histone variants are counterparts of the replication-coupled histone H2A. They are characterized by a unique tripartite structure, consisting of a histone fold, an unstructured linker, and a globular macrodomain. MacroH2A1.1 and macroH2A1.2 are the result of alternative splicing of the MACROH2A1 gene and can have opposing biological functions...
April 11, 2022: Seminars in Cell & Developmental Biology
https://read.qxmd.com/read/35331626/histone-h2a-variants-diversifying-chromatin-to-ensure-genome-integrity
#19
REVIEW
Philipp Oberdoerffer, Kyle M Miller
Histone variants represent chromatin components that diversify the structure and function of the genome. The variants of H2A, primarily H2A.X, H2A.Z and macroH2A, are well-established participants in DNA damage response (DDR) pathways, which function to protect the integrity of the genome. Through their deposition, post-translational modifications and unique protein interaction networks, these variants guard DNA from endogenous threats including replication stress and genome fragility as well as from DNA lesions inflicted by exogenous sources...
March 21, 2022: Seminars in Cell & Developmental Biology
https://read.qxmd.com/read/35120578/multiple-distinct-domains-of-human-xist-are-required-to-coordinate-gene-silencing-and-subsequent-heterochromatin-formation
#20
JOURNAL ARTICLE
Thomas Dixon-McDougall, Carolyn J Brown
BACKGROUND: Mammalian dosage compensation is achieved by the inactivation of one X chromosome in XX individuals. In eutheria this process is initiated early in development by the long non-coding RNA XIST. Studies of the initiation of silencing by XIST have focussed on mouse models, so the domains of XIST required to induce silencing in humans, and their relationship with domains required to establish heterochromatin remain to be determined. METHODS: We have previously established an inducible XIST cDNA in somatic cells and shown it can induce silencing and recruit heterochromatic features...
February 4, 2022: Epigenetics & Chromatin
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