keyword
https://read.qxmd.com/read/38306580/the-dynamic-interplay-between-ribosomal-dna-and-transposable-elements-a-perspective-from-genomics-and-cytogenetics
#21
JOURNAL ARTICLE
Sònia Garcia, Ales Kovarik, Sophie Maiwald, Ludwig Mann, Nicola Schmidt, Joan Pere Pascual-Díaz, Daniel Vitales, Beatrice Weber, Tony Heitkam
Although both are salient features of genomes, at first glance ribosomal DNAs (rDNAs) and transposable elements (TEs) are genetic elements with not much in common: whereas rDNAs are mainly viewed as housekeeping genes that uphold all prime genome functions, TEs are generally portrayed as selfish and disruptive. These opposing characteristics are also mirrored in other attributes: organization in tandem (rDNAs) versus organization in a dispersed manner (TEs); evolution in a concerted manner (rDNAs) versus evolution by diversification (TEs); and activity that prolongs genomic stability (rDNAs) versus activity that shortens it (TEs)...
February 2, 2024: Molecular Biology and Evolution
https://read.qxmd.com/read/38297124/an-epigenetic-barrier-sets-the-timing-of-human-neuronal-maturation
#22
JOURNAL ARTICLE
Gabriele Ciceri, Arianna Baggiolini, Hyein S Cho, Meghana Kshirsagar, Silvia Benito-Kwiecinski, Ryan M Walsh, Kelly A Aromolaran, Alberto J Gonzalez-Hernandez, Hermany Munguba, So Yeon Koo, Nan Xu, Kaylin J Sevilla, Peter A Goldstein, Joshua Levitz, Christina S Leslie, Richard P Koche, Lorenz Studer
The pace of human brain development is highly protracted compared with most other species1-7 . The maturation of cortical neurons is particularly slow, taking months to years to develop adult functions3-5 . Remarkably, such protracted timing is retained in cortical neurons derived from human pluripotent stem cells (hPSCs) during in vitro differentiation or upon transplantation into the mouse brain4,8,9 . Those findings suggest the presence of a cell-intrinsic clock setting the pace of neuronal maturation, although the molecular nature of this clock remains unknown...
January 31, 2024: Nature
https://read.qxmd.com/read/38297077/hnf4a-guides-the-mll4-complex-to-establish-and-maintain-h3k4me1-at-gene-regulatory-elements
#23
JOURNAL ARTICLE
Avinash Thakur, Kwangjin Park, Rebecca Cullum, Bettina M Fuglerud, Mina Khoshnoodi, Sibyl Drissler, Tabea L Stephan, Jeremy Lotto, Donghwan Kim, Frank J Gonzalez, Pamela A Hoodless
Hepatocyte nuclear factor 4A (HNF4A/NR2a1), a transcriptional regulator of hepatocyte identity, controls genes that are crucial for liver functions, primarily through binding to enhancers. In mammalian cells, active and primed enhancers are marked by monomethylation of histone 3 (H3) at lysine 4 (K4) (H3K4me1) in a cell type-specific manner. How this modification is established and maintained at enhancers in connection with transcription factors (TFs) remains unknown. Using analysis of genome-wide histone modifications, TF binding, chromatin accessibility and gene expression, we show that HNF4A is essential for an active chromatin state...
January 31, 2024: Communications Biology
https://read.qxmd.com/read/38288904/sirt7-promotes-hippo-yap-activation-and-cancer-cell-proliferation-in-hepatocellular-carcinoma-via-suppressing-mst1
#24
JOURNAL ARTICLE
Yiying Gu, Cong Ding, Tingzi Yu, Bohao Liu, Wenbin Tang, Zhiqiang Wang, Xiaohui Tang, Gaoshuang Liang, Jinying Peng, Xiangwen Zhang, Zhuan Li
Abnormal activation of the oncogene YAP in the Hippo pathway is a major feature in liver cancer and inactivation of MST1/2 has been shown to be responsible for the overactivation of YAP that led to tumorigenesis. However, mechanisms underlying MST1/2 dysregulation remain poorly understood. RNA-seq analysis and genome (KEGG) pathway enrichment analysis were used to identify genes and pathways that were regulated by SIRT7. qRT-PCR, ChIP, and luciferase assay were used to investigate transcriptional regulation...
January 30, 2024: Cancer Science
https://read.qxmd.com/read/38272889/epigenetic-priming-targets-tumor-heterogeneity-to-shift-transcriptomic-phenotype-of-pancreatic-ductal-adenocarcinoma-towards-a-vitamin-d-susceptible-state
#25
JOURNAL ARTICLE
Bo He, Lauren Stoffel, Clifford Jiajun He, Kumsun Cho, Albert M Li, Haowen Jiang, Brittany M Flowers, Kha The Nguyen, Kelly Wen Wang, Audrey Yixin Zhao, Meng-Ning Zhou, Sofia Ferreira, Laura D Attardi, Jiangbin Ye
As a highly heterogeneous tumor, pancreatic ductal adenocarcinoma (PDAC) exhibits non-uniform responses to therapies across subtypes. Overcoming therapeutic resistance stemming from this heterogeneity remains a significant challenge. Here, we report that Vitamin D-resistant PDAC cells hijacked Vitamin D signaling to promote tumor progression, whereas epigenetic priming with glyceryl triacetate (GTA) and 5-Aza-2'-deoxycytidine (5-Aza) overcame Vitamin D resistance and shifted the transcriptomic phenotype of PDAC toward a Vitamin D-susceptible state...
January 26, 2024: Cell Death & Disease
https://read.qxmd.com/read/38266066/chromatin-remodelers-are-regulators-of-the-tumor-immune-microenvironment
#26
JOURNAL ARTICLE
Apoorvi Chaudhri, Gregory Lizee, Patrick Hwu, Kunal Rai
Immune checkpoint inhibitors show remarkable responses in a wide range of cancers, yet patients develop adaptive resistance. This necessitates the identification of alternate therapies that synergize with immunotherapies. Epigenetic modifiers are potent mediators of tumor intrinsic mechanisms and have been shown to regulate immune response genes, making them prime targets for therapeutic combinations with immune checkpoint inhibitors. Some success has been observed in early clinical studies that combined immunotherapy with agents targeting DNA methylation and histone modification; however, less is known about chromatin remodeler targeted therapies...
January 24, 2024: Cancer Research
https://read.qxmd.com/read/38258329/phase-2-study-of-epigenetic-priming-with-decitabine-followed-by-cytarabine-for-acute-myeloid-leukemia-in-older-patients
#27
JOURNAL ARTICLE
Annie Im, Kevin Quann, Mounzer Agha, Anastasios Raptis, Robert L Redner, Jing-Zhou Hou, Rafic Farah, Kathleen A Dorritie, Alison R Sehgal, Daniel Normolle, Dana H Bovbjerg, Nidhi Aggarwal, James Herman, Konstantinos Lontos, Michael Boyiadzis
Acute myeloid leukemia (AML) in older patients has a poor prognosis, low complete remission (CR) rates, and poor overall survival (OS). Preclinical studies have shown synergistic effects of epigenetic priming with hypomethylating agents followed by cytarabine. Based on these data, we hypothesized that an induction regimen using epigenetic priming with decitabine, followed by cytarabine would be effective and safe in older patients with previously untreated AML. Here, we conducted a phase 2 trial in which older patients with previously untreated AML received an induction regimen consisting of 1 or 2 courses of decitabine 20 mg/m2 intravenously (IV) for 5 days followed by cytarabine 100 mg/m2 continuous IV infusion for 5 days...
January 22, 2024: American Journal of Hematology
https://read.qxmd.com/read/38255759/structural-basis-of-nucleic-acid-recognition-and-6ma-demethylation-by-caenorhabditis-elegans-nmad-1a
#28
JOURNAL ARTICLE
Guohui Shang, Meiting Yang, Min Li, Lulu Ma, Yunlong Liu, Jun Ma, Yiyun Chen, Xue Wang, Shilong Fan, Mengjia Xie, Wei Wu, Shaodong Dai, Zhongzhou Chen
N 6 -methyladenine (6mA) of DNA is an emerging epigenetic mark in the genomes of Chlamydomonas , Caenorhabditis elegans , and mammals recently. Levels of 6mA undergo drastic fluctuation and thus affect fertility during meiosis and early embryogenesis. Here, we showed three complex structures of 6mA demethylase C. elegans NMAD-1A, a canonical isoform of NMAD-1 (F09F7.7). Biochemical results revealed that NMAD-1A prefers 6mA Bubble or Bulge DNAs. Structural studies of NMAD-1A revealed an unexpected "stretch-out" conformation of its Flip2 region, a conserved element that is usually bent over the catalytic center to facilitate substrate base flipping in other DNA demethylases...
January 5, 2024: International Journal of Molecular Sciences
https://read.qxmd.com/read/38255221/micrornas-as-potential-graft-rejection-or-tolerance-biomarkers-and-their-dilemma-in-clinical-routines-behaving-like-devilish-angelic-or-frightening-elements
#29
REVIEW
Isabel Legaz, Víctor Jimenez-Coll, Rosana González-López, Marina Fernández-González, María José Alegría-Marcos, José Antonio Galián, Carmen Botella, Rosa Moya-Quiles, Manuel Muro-Pérez, Alfredo Minguela, Santiago Llorente, Manuel Muro
Allograft rejection is a widespread complication in allograft recipients with chronic kidney disease. Undertreatment of subclinical and clinical rejection and later post-transplant problems are caused by an imperfect understanding of the mechanisms at play and a lack of adequate diagnostic tools. Many different biomarkers have been analyzed and proposed to detect and monitor these crucial events in transplant outcomes. In this sense, microRNAs may help diagnose rejection or tolerance and indicate appropriate treatment, especially in patients with chronic allograft rejection...
January 5, 2024: Biomedicines
https://read.qxmd.com/read/38254784/it-takes-two-to-tango-the-interplay-between-prostate-cancer-and-its-microenvironment-from-an-epigenetic-perspective
#30
REVIEW
Anniek Zaalberg, Elisabeth Pottendorfer, Wilbert Zwart, Andries M Bergman
Prostate cancer is the second most common cancer in men worldwide and is associated with high morbidity and mortality. Consequently, there is an urgent unmet need for novel treatment avenues. In addition to somatic genetic alterations, deviations in the epigenetic landscape of cancer cells and their tumor microenvironment (TME) are critical drivers of prostate cancer initiation and progression. Unlike genomic mutations, epigenetic modifications are potentially reversible. Therefore, the inhibition of aberrant epigenetic modifications represents an attractive and exciting novel treatment strategy for castration-resistant prostate cancer patients...
January 10, 2024: Cancers
https://read.qxmd.com/read/38254205/chromatin-accessibility-and-cell-cycle-progression-are-controlled-by-the-hdac-associated-sin3b-protein-in-murine-hematopoietic-stem-cells
#31
JOURNAL ARTICLE
Alexander Calderon, Tamara Mestvirishvili, Francesco Boccalatte, Kelly V Ruggles, Gregory David
BACKGROUND: Blood homeostasis requires the daily production of millions of terminally differentiated effector cells that all originate from hematopoietic stem cells (HSCs). HSCs are rare and exhibit unique self-renewal and multipotent properties, which depend on their ability to maintain quiescence through ill-defined processes. Defective control of cell cycle progression can eventually lead to bone marrow failure or malignancy. In particular, the molecular mechanisms tying cell cycle re-entry to cell fate commitment in HSCs remain elusive...
January 23, 2024: Epigenetics & Chromatin
https://read.qxmd.com/read/38251898/unravelling%C3%A2-hdac-selectivity-for%C3%A2-erasing-acetyl-mark-on%C3%A2-lys-5-of-histone%C3%A2-h2b
#32
JOURNAL ARTICLE
Shagun Shukla, Sumit Murmu, Tulasiram Mora, Karthigeyan Dhanasekaran, Rajendra P Roy
The reversible acetylation of specific Lysine residues of histones plays crucial role in the epigenetic regulation of chromatin activity. Importantly, perturbations of acetylation-deacetylation dynamics have important implications for cancer and neurological disorders. There are 18 human HDACs including sirtuins. The site-selective acetyl eraser specificity of HDACs is poorly defined. Deciphering the site specificity preference of HDACs from a gamut of lysine in histones may be critical for targeted inhibitor development and delineation of regulatory mechanisms associated with chromatin...
January 22, 2024: Chembiochem: a European Journal of Chemical Biology
https://read.qxmd.com/read/38237590/zfp281-controls-transcriptional-and-epigenetic-changes-promoting-mouse-pluripotent-state-transitions-via-dnmt3-and-tet1
#33
JOURNAL ARTICLE
Xin Huang, Sophie Balmer, Cong Lyu, Yunlong Xiang, Vikas Malik, Hailin Wang, Yu Zhang, Bishuang Cai, Wei Xie, Anna-Katerina Hadjantonakis, Hongwei Zhou, Jianlong Wang
The progression from naive through formative to primed in vitro pluripotent stem cell states recapitulates epiblast development in vivo during the peri-implantation period of mouse embryo development. Activation of the de novo DNA methyltransferases and reorganization of transcriptional and epigenetic landscapes are key events that occur during these pluripotent state transitions. However, the upstream regulators that coordinate these events are relatively underexplored. Here, using Zfp281 knockout mouse and degron knockin cell models, we identify the direct transcriptional activation of Dnmt3a/3b by ZFP281 in pluripotent stem cells...
January 16, 2024: Developmental Cell
https://read.qxmd.com/read/38227896/trex1-inactivation-unleashes-cancer-cell-sting-interferon-signaling-and-promotes-anti-tumor-immunity
#34
JOURNAL ARTICLE
Tetsuo Tani, Haritha Mathsyaraja, Marco Campisi, Ze-Hua Li, Koji Haratani, Caroline G Fahey, Keiichi Ota, Navin R Mahadevan, Yingxiao Shi, Shin Saito, Kei Mizuno, Tran C Thai, Nobunari Sasaki, Mizuki Homme, Choudhury Fabliha B Yusuf, Adam Kashishian, Jipsa Panchal, Min Wang, Benjamin J Wolf, Thanh U Barbie, Cloud P Paweletz, Prafulla C Gokhale, David Liu, Ravindra Uppaluri, Shunsuke Kitajima, Jennifer Cain, David A Barbie
A substantial fraction of cancers evade immune detection by silencing STING (Stimulator of Interferon Genes)-interferon (IFN) signaling. Therapeutic reactivation of this program via STING agonists, epigenetic or DNA damaging therapies can restore anti-tumor immunity in multiple pre-clinical models. Here we show that adaptive induction of three prime exonuclease 1 (TREX1) restrains STING-dependent nucleic acid sensing in cancer cells via its catalytic function in degrading cytosolic DNA. Cancer cell TREX1 expression is coordinately induced with STING by autocrine IFN and downstream STAT1, preventing signal amplification...
January 10, 2024: Cancer Discovery
https://read.qxmd.com/read/38213626/pluripotency-state-transition-of-embryonic-stem-cells-requires-the-turnover-of-histone-chaperone-fact-on-chromatin
#35
JOURNAL ARTICLE
Hang Zhao, Di Li, Xue Xiao, Cuifang Liu, Guifang Chen, Xiaoyu Su, Zhenxin Yan, Shijia Gu, Yizhou Wang, Guohong Li, Jianxun Feng, Wei Li, Ping Chen, Jiayi Yang, Qing Li
The differentiation of embryonic stem cells (ESCs) begins with the transition from the naive to the primed state. The formative state was recently established as a critical intermediate between the two states. Here, we demonstrate the role of the histone chaperone FACT in regulating the naive-to-formative transition. We found that the Q265K mutation in the FACT subunit SSRP1 increased the binding of FACT to histone H3-H4, impaired nucleosome disassembly in vitro , and reduced the turnover of FACT on chromatin in vivo ...
January 19, 2024: IScience
https://read.qxmd.com/read/38211589/pioneer-and-prdm-transcription-factors-coordinate-bivalent-epigenetic-states-to-safeguard-cell-fate
#36
JOURNAL ARTICLE
Satoshi Matsui, Marissa Granitto, Morgan Buckley, Katie Ludwig, Sandra Koigi, Joseph Shiley, William J Zacharias, Christopher N Mayhew, Hee-Woong Lim, Makiko Iwafuchi
Pioneer transcription factors (TFs) regulate cell fate by establishing transcriptionally primed and active states. However, cell fate control requires the coordination of both lineage-specific gene activation and repression of alternative-lineage programs, a process that is poorly understood. Here, we demonstrate that the pioneer TF FOXA coordinates with PRDM1 TF to recruit nucleosome remodeling and deacetylation (NuRD) complexes and Polycomb repressive complexes (PRCs), which establish highly occupied, accessible nucleosome conformation with bivalent epigenetic states, thereby preventing precocious and alternative-lineage gene expression during human endoderm differentiation...
January 4, 2024: Molecular Cell
https://read.qxmd.com/read/38189779/eomes-dependent-mitochondrial-regulation-promotes-survival-of-pathogenic-cd4-t-cells-during-inflammation
#37
JOURNAL ARTICLE
Emeline Joulia, Michaël F Michieletto, Arantxa Agesta, Cindy Peillex, Virginie Girault, Anne-Louise Le Dorze, Romain Peroceschi, Florence Bucciarelli, Marion Szelechowski, Adeline Chaubet, Nawad Hakim, Rémi Marrocco, Emeline Lhuillier, Manuel Lebeurrier, Rafael J Argüello, Abdelhadi Saoudi, Hicham El Costa, Veronique Adoue, Thierry Walzer, Jean-Emmanuel Sarry, Anne S Dejean
The mechanisms whereby Eomes controls tissue accumulation of T cells and strengthens inflammation remain ill-defined. Here, we show that Eomes deletion in antigen-specific CD4+ T cells is sufficient to protect against central nervous system (CNS) inflammation. While Eomes is dispensable for the initial priming of CD4+ T cells, it is required for long-term maintenance of CNS-infiltrating CD4+ T cells. We reveal that the impact of Eomes on effector CD4+ T cell longevity is associated with sustained expression of multiple genes involved in mitochondrial organization and functions...
February 5, 2024: Journal of Experimental Medicine
https://read.qxmd.com/read/38170774/single-cell-joint-profiling-of-multiple-epigenetic-proteins-and-gene-transcription
#38
JOURNAL ARTICLE
Haiqing Xiong, Qianhao Wang, Chen C Li, Aibin He
Sculpting the epigenome with a combination of histone modifications and transcription factor occupancy determines gene transcription and cell fate specification. Here, we first develop uCoTarget, utilizing a split-pool barcoding strategy for realizing ultrahigh-throughput single-cell joint profiling of multiple epigenetic proteins. Through extensive optimization for sensitivity and multimodality resolution, we demonstrate that uCoTarget enables simultaneous detection of five histone modifications (H3K27ac, H3K4me3, H3K4me1, H3K36me3, and H3K27me3) in 19,860 single cells...
January 5, 2024: Science Advances
https://read.qxmd.com/read/38161581/early-chromatin-remodeling-events-in-acutely-stimulated-cd8-t-cells
#39
JOURNAL ARTICLE
Bryan McDonald, Brent Y Chick, Diana C Hargreaves, Susan M Kaech
T cells undergo extensive chromatin remodeling over several days following stimulation through the T cell receptor. However, the kinetics and gene loci targeted by early remodeling events within the first 24 hours of T cell priming to orchestrate effector differentiation have not been well described. We identified that chromatin accessibility is rapidly and extensively remodeled within 1 hour of stimulation of naïve CD8+ T cells, leading to increased global chromatin accessibility at many effector T cell-associated genes that are enriched for AP-1, early growth response (EGR), and nuclear factor of activated T cells (NFAT) binding sites, but this short duration of stimulation is insufficient for commitment to clonal expansion in vivo ...
December 2023: Yale Journal of Biology and Medicine
https://read.qxmd.com/read/38159883/maternal-western-diet-programs-cardiometabolic-dysfunction-and-hypothalamic-inflammation-via-epigenetic-mechanisms-predominantly-in-the-male-offspring
#40
JOURNAL ARTICLE
Mona Elgazzaz, Clara Berdasco, Jone Garai, Melody Baddoo, Shiping Lu, Hisham Daoud, Jovanny Zabaleta, Franck Mauvais-Jarvis, Eric Lazartigues
OBJECTIVE: Maternal exposure during pregnancy is a strong determinant of offspring health outcomes. Such exposure induces changes in the offspring epigenome resulting in gene expression and functional changes. In this study, we investigated the effect of maternal Western hypercaloric diet (HCD) programming during the perinatal period and its effect on neuronal plasticity and cardiometabolic health in adult offspring. METHODS: C57BL/6J dams were fed HCD for 1 month prior to mating with regular diet (RD) sires and kept on the same diet throughout pregnancy and lactation...
December 28, 2023: Molecular Metabolism
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