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https://www.readbyqxmd.com/read/29234324/long-non-coding-rnas-emerging-and-versatile-regulators-in-host-virus-interactions
#1
REVIEW
Xing-Yu Meng, Yuzi Luo, Muhammad Naveed Anwar, Yuan Sun, Yao Gao, Huawei Zhang, Muhammad Munir, Hua-Ji Qiu
Long non-coding RNAs (lncRNAs) are a class of non-protein-coding RNA molecules, which are involved in various biological processes, including chromatin modification, cell differentiation, pre-mRNA transcription and splicing, protein translation, etc. During the last decade, increasing evidence has suggested the involvement of lncRNAs in both immune and antiviral responses as positive or negative regulators. The immunity-associated lncRNAs modulate diverse and multilayered immune checkpoints, including activation or repression of innate immune signaling components, such as interleukin (IL)-8, IL-10, retinoic acid inducible gene I, toll-like receptors 1, 3, and 8, and interferon (IFN) regulatory factor 7, transcriptional regulation of various IFN-stimulated genes, and initiation of the cell apoptosis pathways...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29233296/protein-protein-and-protein-chromatin-interactions-of-ledgf-p75-as-novel-drug-targets
#2
REVIEW
Jolien Blokken, Jan De Rijck, Frauke Christ, Zeger Debyser
Lens epithelium-derived growth factor p75 (LEDGF/p75), a transcriptional co-activator, plays an important role in tethering protein complexes to the chromatin. Through this tethering function LEDGF/p75 is implicated in a diverse set of human diseases including HIV infection and mixed lineage leukemia, an aggressive form of cancer with poor prognosis. Here we provide an overview of recent progress in resolving protein-protein and protein-chromatin interaction mechanisms of LEDGF/p75. This review will focus on two well-characterized domains, the PWWP domain and the integrase binding domain (IBD)...
June 2017: Drug Discovery Today. Technologies
https://www.readbyqxmd.com/read/29233217/chromatin-remodeling-for-transcription
#3
Yahli Lorch, Roger D Kornberg
The nucleosome serves as a general gene repressor, preventing all initiation of transcription except that which is brought about by specific positive regulatory mechanisms. The positive mechanisms begin with chromatin-remodeling by complexes that slide, disrupt, or otherwise alter the structure and organization of nucleosomes. RSC in yeast and its counterpart PBAF in human cells are the major remodeling complexes for transcription. RSC creates a nucleosome-free region in front of a gene, flanked by strongly positioned +1 and -1 nucleosomes, with the transcription start site typically 10-15 bp inside the border of the +1 nucleosome...
January 2017: Quarterly Reviews of Biophysics
https://www.readbyqxmd.com/read/29232693/host-factors-that-promote-retrotransposon-integration-are-similar-in-distantly-related-eukaryotes
#4
Sudhir Kumar Rai, Maya Sangesland, Michael Lee, Caroline Esnault, Yujin Cui, Atreyi Ghatak Chatterjee, Henry L Levin
Retroviruses and Long Terminal Repeat (LTR)-retrotransposons have distinct patterns of integration sites. The oncogenic potential of retrovirus-based vectors used in gene therapy is dependent on the selection of integration sites associated with promoters. The LTR-retrotransposon Tf1 of Schizosaccharomyces pombe is studied as a model for oncogenic retroviruses because it integrates into the promoters of stress response genes. Although integrases (INs) encoded by retroviruses and LTR-retrotransposons are responsible for catalyzing the insertion of cDNA into the host genome, it is thought that distinct host factors are required for the efficiency and specificity of integration...
December 12, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/29231137/therapeutic-role-of-harmalol-targeting-nucleic-acids-biophysical-perspective-and-in-vitro-cytotoxicity
#5
Sarita Sarkar, Kakali Bhadra
BACKGROUND: Harmalol, a beta carboline alkaloid, shows remarkable importance in the contemporary biomedical research and drug discovery programs. With time, there is growing interest in search for anti-cancer drugs of plant origin with high efficacy, low toxicity and minimum side effects. Most of the chemotherapeutic agents due to their non-selective nature and dose limiting toxicity, use is often restricted, necessitating search for newer drugs having greater potentiality. OBJECTIVE: The review highlighted the interaction of harmalol with nucleic acids of different motifs as sole target biomolecules and in vitro cytotoxicity of the alkaloid in human cancer cell lines with special emphasis on its apoptotic induction ability...
December 11, 2017: Mini Reviews in Medicinal Chemistry
https://www.readbyqxmd.com/read/29229981/the-mating-type-locus-protein-mat1-2-1-of-trichoderma-reesei-interacts-with-xyr1-and-regulates-cellulase-gene-expression-in-response-to-light
#6
Fanglin Zheng, Yanli Cao, Lei Wang, Xinxing Lv, Xiangfeng Meng, Weixin Zhang, Guanjun Chen, Weifeng Liu
Cellulase production in the model cellulolytic fungus Trichoderma reesei is subject to a variety of environmental and physiological conditions involving an intricate regulatory network with multiple transcription factors. Here, we identified the mating type locus protein MAT1-2-1 as an interacting partner for the key transcriptional activator Xyr1 of T. reesei cellulase genes. Yeast two-hybrid and GST pulldown analyses revealed that MAT1-2-1 directly interacted with the putative transcription activation domain (AD, 767~940 aa) and the middle homology region (MHR2, 314~632 aa) of Xyr1...
December 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29229929/oestrogen-receptor-%C3%AE-binds-the-foxp3-promoter-and-modulates-regulatory-t-cell-function-in-human-cervical-cancer
#7
Sreenivas Adurthi, Mahesh M Kumar, H S Vinodkumar, Geetashree Mukherjee, H Krishnamurthy, K Kshitish Acharya, U D Bafna, Devi K Uma, B Abhishekh, Sudhir Krishna, A Parchure, Murali Alka, R S Jayshree
Oestrogen controls Foxp3 expression in regulatory T cells (Treg cells) via a mechanism thought to involve oestrogen receptor alpha (ERα), but the molecular basis and functional impact of ERα signalling in Treg cells remain unclear. We report that ERα ligand oestradiol (E2) is significantly increased in human cervical cancer (CxCa) tissues and tumour-infiltrating Treg cells (CD4+CD25hiCD127low), whereas blocking ERα with the antagonist ICI 182,780 abolishes FOXP3 expression and impairs the function of CxCa infiltrating Treg cells...
December 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29228664/chromatin-remodeling-protein-morc2-promotes-breast-cancer-invasion-and-metastasis-through-a-prd-domain-mediated-interaction-with-ctnnd1
#8
Xiao-Hong Liao, Ye Zhang, Wen-Jie Dong, Zhi-Min Shao, Da-Qiang Li
MORC family CW-type zinc finger 2 (MORC2) is a newly identified chromatin remodeling protein with emerging roles in the regulation of DNA damage response and gene transcription, but its mechanistic role in breast cancer development and progression remains unexplored. Here, we show that MORC2 promoted breast cancer invasion and metastasis and these effects depended on a proline-rich domain (PRD) within its carboxy-terminal region spanning residues 601-734. Induced expression of wild-type MORC2 did not significantly affect cell proliferation and cell-cycle progression, but promoted breast cancer cell migration and invasion in vitro and metastatic lung colonization in vivo...
November 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29228550/regulation-of-xpc-deubiquitination-by-usp11-in-repair-of-uv-induced-dna-damage
#9
Palak Shah, Lei Qiang, Seungwon Yang, Keyoumars Soltani, Yu-Ying He
Nucleotide excision repair (NER) is the most versatile DNA repair pathway for removing DNA damage caused by UV radiation and many environmental carcinogens. NER is essential for suppressing tumorigenesis in the skin, lungs and brain. Although the core NER proteins have been identified and characterized, molecular regulation of NER remains poorly understood. Here we show that ubiquitin-specific peptidase 11 (USP11) positively regulates NER by deubiquitinating xeroderma pigmentosum complementation group C (XPC) and promoting its retention at the DNA damage sites...
November 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/29227354/current-views-on-the-pathogenesis-of-sjgren-s-syndrome
#10
Elena Pontarini, Davide Lucchesi, Michele Bombardieri
PURPOSE OF REVIEW: The purpose of this review is to provide an insight into the pathophysiological mechanisms involved in the pathogenesis of primary Sjgren's Syndrome (pSS), highlighting recent findings with potential therapeutic repercussions. RECENT FINDINGS: In the last 2 years, epigenetic analyses provided new insights into pSS pathogenesis. Characterization of DNA methylation patterns, chromatin structures and microRNA confirmed the importance of aberrant interferon and B-cell responses in the development of the disease...
December 8, 2017: Current Opinion in Rheumatology
https://www.readbyqxmd.com/read/29227193/ddx5-p68-associated-lncrna-loc284454-is-differentially-expressed-in-human-cancers-and-modulates-gene-expression
#11
Monalisa Das, Arun Renganathan, Shrinivas Nivrutti Dighe, Utsa Bhaduri, Abhijith Shettar, Geetashree Mukherjee, Paturu Kondaiah, Manchanahalli R Satyanarayana Rao
Long non-coding RNAs (lncRNAs) are emerging as important players in regulation of gene expression in higher eukaryotes. DDX5/p68 RNA helicase protein which is involved in splicing of precursor mRNAs also interacts with lncRNAs like, SRA and mrhl, to modulate gene expression. We performed RIP-seq analysis in HEK293T cells to identify the complete repertoire of DDX5/p68 interacting transcripts including 73 single exonic (SE) lncRNAs. The LOC284454 lncRNA is the second top hit of the list of SE lncRNAs which we have characterized in detail for its molecular features and cellular functions...
December 11, 2017: RNA Biology
https://www.readbyqxmd.com/read/29226473/contributions-to-nucleosome-dynamics-in-chromatin-from-interactive-propagation-of-phosphorylation-acetylation-and-inducible-histone-lysine-basicities
#12
Lois R Manning, James M Manning
The effect of phosphorylation on the basicities of amines in histone H3 peptides and their acetylation kinetics is probed with a mild chemical acetylating agent. Phosphorylation of Ser-10 lowers the rate of chemical acetylation of Lys-9, Lys-14 and Lys-18 by methyl acetyl phosphate in that order consistent with a higher pKa of these Lys residues induced by phosphorylation; basicities increase up to 3 pKa units as a function of distance from Ser-10 phosphate. Enzymic acetylation of Lys residues with high pKa values in nucleosomes is also expected to be enhanced by phosphorylation, consistent with the known mechanism involving binding of protonated amines to N-acetyltransferases; fetal hemoglobin has a related linkage of increased basicity at a specific site, its acetylation, and a resulting decrease in subunit interaction strength...
December 11, 2017: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/29224149/nucleosome-occupancy-and-methylome-sequencing-nome-seq
#13
Fides D Lay, Theresa K Kelly, Peter A Jones
Various methodologies are available to interrogate specific components of epigenetic mechanisms such as DNA methylation or nucleosome occupancy at both the locus-specific and the genome-wide level. It has become increasingly clear, however, that comprehension of the functional interactions between epigenetic mechanisms is critical for understanding how cellular transcription programs are regulated or deregulated during normal and disease development. The Nucleosome Occupancy and Methylome sequencing (NOMe-seq) assay allows us to directly measure the relationship between DNA methylation and nucleosome occupancy by taking advantage of the methyltransferase M...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29224136/a-summary-of-the-biological-processes-disease-associated-changes-and-clinical-applications-of-dna-methylation
#14
Gitte Brinch Andersen, Jörg Tost
DNA methylation at cytosines followed by guanines, CpGs, forms one of the multiple layers of epigenetic mechanisms controlling and modulating gene expression through chromatin structure. It closely interacts with histone modifications and chromatin remodeling complexes to form the local genomic and higher-order chromatin landscape. DNA methylation is essential for proper mammalian development, crucial for imprinting and plays a role in maintaining genomic stability. DNA methylation patterns are susceptible to change in response to environmental stimuli such as diet or toxins, whereby the epigenome seems to be most vulnerable during early life...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29224078/investigate-global-chromosomal-interaction-by-hi-c-in-human-naive-cd4-t-cells
#15
Xiangzhi Meng, Nicole Riley, Ryan Thompson, Siddhartha Sharma
Hi-C is a methodology developed to reveal chromosomal interactions from a genome-wide perspective. Here, we described a protocol for generating Hi-C sequencing libraries in resting and activated human naive CD4 T cells to investigate activation-induced chromatin structure re-arrangement in T cell activation followed by a section reviewing the general concepts of Hi-C data analysis.
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29221147/long-noncoding-rna-linc00673-epigenetically-suppresses-klf4-by-interacting-with-ezh2-and-dnmt1-in-gastric-cancer
#16
Ming-Chen Ba, Hui Long, Shu-Zhong Cui, Yuan-Feng Gong, Zhao-Fei Yan, Yin-Bing Wu, Yi-Nuo Tu
Long non-coding RNAs (lncRNAs), a variety of transcripts without protein coding ability, have recently been reported to play vital roles in gastric cancer (GC) development and progression. However, the biological role of long non-coding RNA LINC00673 in GC is not fully known. In the study, we found that LINC00673 expression was dramatically higher in gastric cancer tissues compared with adjacent normal tissues, and positively associated with lymph node metastasis, distant metastasis and TNM stage in patients...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29220657/hnrnpk-recruits-pcgf3-5-prc1-to-the-xist-rna-b-repeat-to-establish-polycomb-mediated-chromosomal-silencing
#17
Greta Pintacuda, Guifeng Wei, Chloë Roustan, Burcu Anil Kirmizitas, Nicolae Solcan, Andrea Cerase, Alfredo Castello, Shabaz Mohammed, Benoît Moindrot, Tatyana B Nesterova, Neil Brockdorff
The Polycomb-repressive complexes PRC1 and PRC2 play a key role in chromosome silencing induced by the non-coding RNA Xist. Polycomb recruitment is initiated by the PCGF3/5-PRC1 complex, which catalyzes chromosome-wide H2A lysine 119 ubiquitylation, signaling recruitment of other PRC1 complexes, and PRC2. However, the molecular mechanism for PCGF3/5-PRC1 recruitment by Xist RNA is not understood. Here we define the Xist RNA Polycomb Interaction Domain (XR-PID), a 600 nt sequence encompassing the Xist B-repeat element...
December 7, 2017: Molecular Cell
https://www.readbyqxmd.com/read/29220653/a-poly-adp-ribose-trigger-releases-the-auto-inhibition-of-a-chromatin-remodeling-oncogene
#18
Hari R Singh, Aurelio P Nardozza, Ingvar R Möller, Gunnar Knobloch, Hans A V Kistemaker, Markus Hassler, Nadine Harrer, Charlotte Blessing, Sebastian Eustermann, Christiane Kotthoff, Sébastien Huet, Felix Mueller-Planitz, Dmitri V Filippov, Gyula Timinszky, Kasper D Rand, Andreas G Ladurner
DNA damage triggers chromatin remodeling by mechanisms that are poorly understood. The oncogene and chromatin remodeler ALC1/CHD1L massively decompacts chromatin in vivo yet is inactive prior to DNA-damage-mediated PARP1 induction. We show that the interaction of the ALC1 macrodomain with the ATPase module mediates auto-inhibition. PARP1 activation suppresses this inhibitory interaction. Crucially, release from auto-inhibition requires a poly-ADP-ribose (PAR) binding macrodomain. We identify tri-ADP-ribose as a potent PAR-mimic and synthetic allosteric effector that abrogates ATPase-macrodomain interactions, promotes an ungated conformation, and activates the remodeler's ATPase...
December 7, 2017: Molecular Cell
https://www.readbyqxmd.com/read/29220652/mechanistic-insights-into-autoinhibition-of-the-oncogenic-chromatin-remodeler-alc1
#19
Laura C Lehmann, Graeme Hewitt, Shintaro Aibara, Alexander Leitner, Emil Marklund, Sarah L Maslen, Varun Maturi, Yang Chen, David van der Spoel, J Mark Skehel, Aristidis Moustakas, Simon J Boulton, Sebastian Deindl
Human ALC1 is an oncogene-encoded chromatin-remodeling enzyme required for DNA repair that possesses a poly(ADP-ribose) (PAR)-binding macro domain. Its engagement with PARylated PARP1 activates ALC1 at sites of DNA damage, but the underlying mechanism remains unclear. Here, we establish a dual role for the macro domain in autoinhibition of ALC1 ATPase activity and coupling to nucleosome mobilization. In the absence of DNA damage, an inactive conformation of the ATPase is maintained by juxtaposition of the macro domain against predominantly the C-terminal ATPase lobe through conserved electrostatic interactions...
December 7, 2017: Molecular Cell
https://www.readbyqxmd.com/read/29218911/convergent-downstream-candidate-mechanisms-of-independent-intergenic-polymorphisms-between-co-classified-diseases-implicate-epistasis-among-noncoding-elements
#20
Jiali Han, Jianrong Li, Ikbel Achour, Lorenzo Pesce, Ian Foster, Haiquan Li, Yves A Lussier
Eighty percent of DNA outside protein coding regions was shown biochemically functional by the ENCODE project, enabling studies of their interactions. Studies have since explored how convergent downstream mechanisms arise from independent genetic risks of one complex disease. However, the cross-talk and epistasis between intergenic risks associated with distinct complex diseases have not been comprehensively characterized. Our recent integrative genomic analysis unveiled downstream biological effectors of disease-specific polymorphisms buried in intergenic regions, and we then validated their genetic synergy and antagonism in distinct GWAS...
2018: Pacific Symposium on Biocomputing
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