keyword
https://read.qxmd.com/read/38493346/incorporating-network-diffusion-and-peak-location-information-for-better-single-cell-atac-seq-data-analysis
#1
JOURNAL ARTICLE
Jiating Yu, Jiacheng Leng, Zhichao Hou, Duanchen Sun, Ling-Yun Wu
Single-cell assay for transposase-accessible chromatin using sequencing (scATAC-seq) data provided new insights into the understanding of epigenetic heterogeneity and transcriptional regulation. With the increasing abundance of dataset resources, there is an urgent need to extract more useful information through high-quality data analysis methods specifically designed for scATAC-seq. However, analyzing scATAC-seq data poses challenges due to its near binarization, high sparsity and ultra-high dimensionality properties...
January 22, 2024: Briefings in Bioinformatics
https://read.qxmd.com/read/38493342/scencore-leveraging-single-cell-epigenetic-data-to-predict-chromatin-conformation-using-graph-embedding
#2
JOURNAL ARTICLE
Ziheng Duan, Siwei Xu, Shushrruth Sai Srinivasan, Ahyeon Hwang, Che Yu Lee, Feng Yue, Mark Gerstein, Yu Luan, Matthew Girgenti, Jing Zhang
Dynamic compartmentalization of eukaryotic DNA into active and repressed states enables diverse transcriptional programs to arise from a single genetic blueprint, whereas its dysregulation can be strongly linked to a broad spectrum of diseases. While single-cell Hi-C experiments allow for chromosome conformation profiling across many cells, they are still expensive and not widely available for most labs. Here, we propose an alternate approach, scENCORE, to computationally reconstruct chromatin compartments from the more affordable and widely accessible single-cell epigenetic data...
January 22, 2024: Briefings in Bioinformatics
https://read.qxmd.com/read/38490199/enhancer-promoter-interactions-are-reconfigured-through-the-formation-of-long-range-multiway-hubs-as-mouse-es-cells-exit-pluripotency
#3
JOURNAL ARTICLE
David Lando, Xiaoyan Ma, Yang Cao, Aleksandra Jartseva, Tim J Stevens, Wayne Boucher, Nicola Reynolds, Bertille Montibus, Dominic Hall, Andreas Lackner, Ramy Ragheb, Martin Leeb, Brian D Hendrich, Ernest D Laue
Enhancers bind transcription factors, chromatin regulators, and non-coding transcripts to modulate the expression of target genes. Here, we report 3D genome structures of single mouse ES cells as they are induced to exit pluripotency and transition through a formative stage prior to undergoing neuroectodermal differentiation. We find that there is a remarkable reorganization of 3D genome structure where inter-chromosomal intermingling increases dramatically in the formative state. This intermingling is associated with the formation of a large number of multiway hubs that bring together enhancers and promoters with similar chromatin states from typically 5-8 distant chromosomal sites that are often separated by many Mb from each other...
March 5, 2024: Molecular Cell
https://read.qxmd.com/read/38490161/rna-in-chromatin-organization-and-nuclear-architecture
#4
REVIEW
Maierdan Palihati, Noriko Saitoh
In the cell nucleus, genomic DNA is surrounded by nonmembranous nuclear bodies. This might result from specific regions of the genome being transcribed into long noncoding RNAs (lncRNAs), which tend to remain at the sites of their own transcription. The lncRNAs seed the nuclear bodies by recruiting and concentrating proteins and RNAs, which undergo liquid-liquid-phase separation, and form molecular condensates, the so-called nuclear bodies. These nuclear bodies may provide appropriate environments for gene activation or repression...
March 14, 2024: Current Opinion in Genetics & Development
https://read.qxmd.com/read/38490101/enhancer-infestation-drives-tumorigenic-activation-of-inactive-b-compartment-in-epstein-barr-virus-positive-nasopharyngeal-carcinoma
#5
JOURNAL ARTICLE
Harue Mizokami, Atsushi Okabe, Ruchi Choudhary, Masato Mima, Kenta Saeda, Masaki Fukuyo, Bahityar Rahmutulla, Motoaki Seki, Boon-Cher Goh, Satoru Kondo, Hirotomo Dochi, Makiko Moriyama-Kita, Kiyoshi Misawa, Toyoyuki Hanazawa, Patrick Tan, Tomokazu Yoshizaki, Melissa Jane Fullwood, Atsushi Kaneda
BACKGROUND: Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV)-associated malignant epithelial tumor endemic to Southern China and Southeast Asia. While previous studies have revealed a low frequency of gene mutations in NPC, its epigenomic aberrations are not fully elucidated apart from DNA hypermethylation. Epigenomic rewiring and enhancer dysregulation, such as enhancer hijacking due to genomic structural changes or extrachromosomal DNA, drive cancer progression. METHODS: We conducted Hi-C, 4C-seq, ChIP-seq, and RNA-seq analyses to comprehensively elucidate the epigenome and interactome of NPC using C666-1 EBV(+)-NPC cell lines, NP69T immortalized nasopharyngeal epithelial cells, clinical NPC biopsy samples, and in vitro EBV infection in HK1 and NPC-TW01 EBV(-) cell lines...
March 14, 2024: EBioMedicine
https://read.qxmd.com/read/38489486/multi-omics-analysis-reveals-epigenetically-regulated-processes-and-patient-classification-in-lung-adenocarcinoma
#6
JOURNAL ARTICLE
Anastasia Brativnyk, Jørgen Ankill, Åslaug Helland, Thomas Fleischer
Aberrant DNA methylation is a hallmark of many cancer types. Despite our knowledge of epigenetic and transcriptomic alterations in lung adenocarcinoma (LUAD), we lack robust multi-modal molecular classifications for patient stratification. This is partly because the impact of epigenetic alterations on lung cancer development and progression is still not fully understood. To that end, we identified disease-associated processes under epigenetic regulation in LUAD. We performed a genome-wide expression-methylation Quantitative Trait Loci (emQTL) analysis by integrating DNA methylation and gene expression data from 453 patients in the TCGA cohort...
March 15, 2024: International Journal of Cancer. Journal International du Cancer
https://read.qxmd.com/read/38489381/transcription-induced-active-forces-suppress-chromatin-motion
#7
JOURNAL ARTICLE
Sucheol Shin, Guang Shi, Hyun Woo Cho, D Thirumalai
The organization of interphase chromosomes in a number of species is starting to emerge thanks to advances in a variety of experimental techniques. However, much less is known about the dynamics, especially in the functional states of chromatin. Some experiments have shown that the motility of individual loci in human interphase chromosome decreases during transcription and increases upon inhibiting transcription. This is a counterintuitive finding because it is thought that the active mechanical force ( F ) on the order of ten piconewtons, generated by RNA polymerase II (RNAPII) that is presumably transmitted to the gene-rich region of the chromatin, would render it more open, thus enhancing the mobility...
March 19, 2024: Proceedings of the National Academy of Sciences of the United States of America
https://read.qxmd.com/read/38487270/timeless-tipin-interactions-with-mcm-and-rpa-mediate-dna-replication-stress-response
#8
JOURNAL ARTICLE
Paulina Prorok, Eva Wolf, M Cristina Cardoso
The accuracy of replication is one of the most important mechanisms ensuring the stability of the genome. The fork protection complex prevents premature replisome stalling and/or premature disassembly upon stress. Here, we characterize the Timeless-Tipin complex, a component of the fork protection complex. We used microscopy approaches, including colocalization analysis and proximity ligation assay, to investigate the spatial localization of the complex during ongoing replication in human cells. Taking advantage of the replication stress induction and the ensuing polymerase-helicase uncoupling, we characterized the Timeless-Tipin localization within the replisome...
2024: Frontiers in Cell and Developmental Biology
https://read.qxmd.com/read/38486454/dissecting-the-molecular-basis-of-spike-traits-by-integrating-gene-regulatory-network-and-genetic-variation-in-wheat
#9
JOURNAL ARTICLE
Guo Ai, Chao He, Siteng Bi, Ziru Zhou, Ankui Liu, Xin Hu, Yanyan Liu, Liujie Jin, JiaCheng Zhou, Heping Zhang, Dengxiang Du, Hao Chen, Xin Gong, Sulaiman Saeed, Handong Su, Caixia Lan, Wei Chen, Qiang Li, Hailiang Mao, Lin Li, Hao Liu, Dijun Chen, Kerstin Kaufmann, Khaled F Alazab, Wenhao Yan
Spike architecture influences both grain weight and grain number per spike, which are the two major components of grain yield in bread wheat (Triticum aestivum L.). However, the complex wheat genome and the influence of various environmental factors pose challenges in mapping the causal genes affecting the spike traits. Here, we systematically identify genes involved in spike trait formation by integrating the information of genomic variation and gene regulatory network (GRN) controlling young spike development in wheat...
March 14, 2024: Plant communications
https://read.qxmd.com/read/38485770/txnip-regulates-the-oct4-mediated-pluripotency-circuitry-via-metabolic-changes-upon-differentiation
#10
JOURNAL ARTICLE
Sojung Kwak, Cho Lok Song, Yee Sook Cho, Inpyo Choi, Jae-Eun Byun, Haiyoung Jung, Jungwoon Lee
Thioredoxin interacting protein (Txnip) is a stress-responsive factor regulating Trx1 for redox balance and involved in diverse cellular processes including proliferation, differentiation, apoptosis, inflammation, and metabolism. However, the biological role of Txnip function in stem cell pluripotency has yet to be investigated. Here, we reveal the novel functions of mouse Txnip in cellular reprogramming and differentiation onset by involving in glucose-mediated histone acetylation and the regulation of Oct4, which is a fundamental component of the molecular circuitry underlying pluripotency...
March 15, 2024: Cellular and Molecular Life Sciences: CMLS
https://read.qxmd.com/read/38484732/the-sirtuin-associated-human-senescence-program-converges-on-the-activation-of-placenta-specific-gene-pappa
#11
JOURNAL ARTICLE
Shijia Bi, Xiaoyu Jiang, Qianzhao Ji, Zehua Wang, Jie Ren, Si Wang, Yang Yu, Ruoqi Wang, Zunpeng Liu, Junhang Liu, Jianli Hu, Guoqiang Sun, Zeming Wu, Zhiqing Diao, Jingyi Li, Liang Sun, Juan Carlos Izpisua Belmonte, Weiqi Zhang, Guang-Hui Liu, Jing Qu
Sirtuins are pro-longevity genes with chromatin modulation potential, but how these properties are connected is not well understood. Here, we generated a panel of isogeneic human stem cell lines with SIRT1-SIRT7 knockouts and found that any sirtuin deficiency leads to accelerated cellular senescence. Through large-scale epigenomic analyses, we show how sirtuin deficiency alters genome organization and that genomic regions sensitive to sirtuin deficiency are preferentially enriched in active enhancers, thereby promoting interactions within topologically associated domains and the formation of de novo enhancer-promoter loops...
March 11, 2024: Developmental Cell
https://read.qxmd.com/read/38484065/fork-coupling-directs-dna-replication-elongation-and-termination
#12
JOURNAL ARTICLE
Yang Liu, Zhengrong Zhangding, Xuhao Liu, Tingting Gan, Chen Ai, Jinchun Wu, Haoxin Liang, Mohan Chen, Yuefeng Guo, Rusen Lu, Yongpeng Jiang, Xiong Ji, Ning Gao, Daochun Kong, Qing Li, Jiazhi Hu
DNA replication is initiated at multiple loci to ensure timely duplication of eukaryotic genomes. Sister replication forks progress bidirectionally, and replication terminates when two convergent forks encounter one another. To investigate the coordination of replication forks, we developed a replication-associated in situ HiC method to capture chromatin interactions involving nascent DNA. We identify more than 2000 fountain-like structures of chromatin contacts in human and mouse genomes, indicative of coupling of DNA replication forks...
March 15, 2024: Science
https://read.qxmd.com/read/38483766/investigation-of-the-mutual-crosstalk-between-er-stress-and-pi3k-akt-mtor-signaling-pathway-in-iron-overload-induced-liver-injury-in-chicks
#13
JOURNAL ARTICLE
Xiang-Long Lv, Wen-Lei Li, Feng-Jiao Sun, Yu-Zhi An, Ning Sun, Xiao-Ping Lv, Xue-Li Gao
Iron is an essential element for the normal functioning of living organisms, but excessive iron deposition can lead to organ damage. This study aims to investigate the interaction between the endoplasmic reticulum stress signaling pathway and the PI3K/AKT/mTOR signaling pathway in liver injury induced by iron overload in chicks. Rspectively, 150 one-day-old broilers were divided into three groups and supplemented with 50 (C), 500 (E1), and 1000 (E2) mg ferrous sulfate monohydrate/kg in the basal diet. Samples were taken after continuous feeding for 14 days...
March 14, 2024: Biometals: An International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine
https://read.qxmd.com/read/38482865/anp32e-binds-histone-h2a-z-in-a-cell-cycle-dependent-manner-and-regulates-its-protein-stability-in-the-cytoplasm
#14
JOURNAL ARTICLE
Yasmin Dijkwel, Gene Hart-Smith, Sebastian Kurscheid, David J Tremethick
ANP32e, a chaperone of H2A.Z, is receiving increasing attention because of its association with cancer growth and progression. An unanswered question is whether ANP32e regulates H2A.Z dynamics during the cell cycle; this could have clear implications for the proliferation of cancer cells. We confirmed that ANP32e regulates the growth of human U2OS cancer cells and preferentially interacts with H2A.Z during the G1 phase of the cell cycle. Unexpectedly, ANP32e does not mediate the removal of H2A.Z from chromatin, is not a stable component of the p400 remodeling complex and is not strongly associated with chromatin...
March 14, 2024: Molecular and Cellular Biology
https://read.qxmd.com/read/38482729/mechanical-memory-based-on-chromatin-and-metabolism-remodeling-promotes-proliferation-and-smooth-muscle-differentiation-in-mesenchymal-stem-cells
#15
JOURNAL ARTICLE
Jing Na, Qiusheng Shi, Zhijie Yang, Yu Liu, Xinyuan Chen, Ziyi Wang, Lisha Zheng, Yubo Fan
Stem cells respond and remember mechanical cues from the microenvironment, which modulates their therapeutic effects. Chromatin organization and energy metabolism regulate the stem cell fate induced by mechanical cues. However, the mechanism of mechanical memory is still unclear. This study aimed to investigate the effects of mechanical amplitude, frequency, duration, and stretch cycle on mechanical memory in mesenchymal stem cells. It showed that the amplitude was the dominant parameter to the persistence of cell alignment...
March 31, 2024: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://read.qxmd.com/read/38482131/nonpathogenic-leaf-colonizing-bacteria-elicit-pathogen-like-responses-in-a-colonization-density-dependent-manner
#16
JOURNAL ARTICLE
Moritz Miebach, Léa Faivre, Daniel Schubert, Paula Jameson, Mitja Remus-Emsermann
Leaves are colonized by a complex mix of microbes, termed the leaf microbiota. Even though the leaf microbiota is increasingly recognized as an integral part of plant life and health, our understanding of its interactions with the plant host is still limited. Here, mature, axenically grown Arabidopsis thaliana plants were spray inoculated with six diverse leaf-colonizing bacteria. The transcriptomic changes in leaves were tracked over time and significant changes in ethylene marker ( ARL2 ) expression were observed only 2-4 days after spray inoculation...
April 2024: Plant Environ Interact
https://read.qxmd.com/read/38481679/apabetalone-rvx-208-a-potential-epigenetic-therapy-for-the-treatment-of-cardiovascular-renal-neurological-viral-and-cancer-disorders
#17
REVIEW
Hevna Dhulkifle, Mohammad Issam Diab, Majed Algonaiah, Hesham M Korashy, Zaid H Maayah
Bromodomain and extra-terminal domain proteins (BET proteins) are epigenetic reader proteins that have been implicated in regulating gene expression through binding to chromatin and interaction with transcription factors. These proteins are located in the nucleus and are responsible for recognizing acetylated lysine residues on histones, reading epigenetic messages, recruiting key transcription factors, and thereby regulating gene expression. BET proteins control the transcription of genes responsible for maladaptive effects in inflammation, cancer, and renal and cardiovascular diseases...
March 8, 2024: ACS Pharmacology & Translational Science
https://read.qxmd.com/read/38480902/dysregulated-creb3-cleavage-at-the-nuclear-membrane-induces-karyoptosis-mediated-cell-death
#18
JOURNAL ARTICLE
Ga-Eun Lee, Geul Bang, Jiin Byun, Cheol-Jung Lee, Weidong Chen, Dohyun Jeung, Hyun-Jung An, Han Chang Kang, Joo Young Lee, Hye Suk Lee, Young-Soo Hong, Dae Joon Kim, Megan Keniry, Jin Young Kim, Jin-Sung Choi, Manolis Fanto, Sung-Jun Cho, Kwang-Dong Kim, Yong-Yeon Cho
Cancer cells often exhibit resistance to apoptotic cell death, but they may be vulnerable to other types of cell death. Elucidating additional mechanisms that govern cancer cell death is crucial for developing new therapies. Our research identified cyclic AMP-responsive element-binding protein 3 (CREB3) as a crucial regulator and initiator of a unique cell death mechanism known as karyoptosis. This process is characterized by nuclear shrinkage, deformation, and the loss of nuclear components following nuclear membrane rupture...
March 13, 2024: Experimental & Molecular Medicine
https://read.qxmd.com/read/38479789/primary-osteoarthritis-chondrocyte-map-of-chromatin-conformation-reveals-novel-candidate-effector-genes
#19
JOURNAL ARTICLE
Norbert Bittner, Chenfu Shi, Danyun Zhao, James Ding, Lorraine Southam, Diane Swift, Peter Kreitmaier, Mauro Tutino, Odysseas Stergiou, Jackson T S Cheung, Georgia Katsoula, Jenny Hankinson, Jeremy Mark Wilkinson, Gisela Orozco, Eleftheria Zeggini
OBJECTIVES: Osteoarthritis is a complex disease with a huge public health burden. Genome-wide association studies (GWAS) have identified hundreds of osteoarthritis-associated sequence variants, but the effector genes underpinning these signals remain largely elusive. Understanding chromosome organisation in three-dimensional (3D) space is essential for identifying long-range contacts between distant genomic features (e.g., between genes and regulatory elements), in a tissue-specific manner...
March 13, 2024: Annals of the Rheumatic Diseases
https://read.qxmd.com/read/38478142/bmsc-derived-exosomes-carrying-mir-26a-5p-ameliorate-spinal-cord-injury-via-negatively-regulating-ezh2-and-activating-the-bdnf-trkb-creb-signaling
#20
JOURNAL ARTICLE
Min Chen, Yu Lin, Wenbin Guo, Lihui Chen
BACKGROUND: Spinal cord injury (SCI) is a destructive neurological and pathological state that causes major motor, sensory and autonomic dysfunctions. Bone marrow mesenchymal stem cells (BMSCs)-derived exosomes show great therapeutic potential for SCI. Exosomes derived from miR-26a-modified MSCs promote axonal regeneration following SCI. Our study aims to uncover the mechanisms by which BMSC-derived exosomes carrying miR-26a-5p regulate SCI. METHODS: BMSCs and BMSC-derived exosomes were isolated and characterized by Oil Red O and alizarin red staining, transmission electron microscopy, flow cytometry, nanoparticle tracking analysis and Western blotting...
March 13, 2024: Molecular Neurobiology
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