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Histone demethylation

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https://www.readbyqxmd.com/read/29343972/targeting-histone-methyltransferase-and-demethylase-in-acute-myeloid-leukemia-therapy
#1
REVIEW
Germana Castelli, Elvira Pelosi, Ugo Testa
Acute myeloid leukemia (AML) is a clonal disorder of myeloid progenitors characterized by the acquisition of chromosomal abnormalities, somatic mutations, and epigenetic changes that determine a consistent degree of biological and clinical heterogeneity. Advances in genomic technologies have increasingly shown the complexity and heterogeneity of genetic and epigenetic alterations in AML. Among the genetic alterations occurring in AML, frequent are the genetic alterations at the level of various genes involved in the epigenetic control of the DNA methylome and histone methylome...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29339836/the-role-of-metabolic-enzymes-in-mesenchymal-tumors-and-tumor-syndromes-genetics-pathology-and-molecular-mechanisms
#2
REVIEW
Inga-Marie Schaefer, Jason L Hornick, Judith V M G Bovée
The discovery of mutations in genes encoding the metabolic enzymes isocitrate dehydrogenase (IDH), succinate dehydrogenase (SDH), and fumarate hydratase (FH) has expanded our understanding not only of altered metabolic pathways but also epigenetic dysregulation in cancer. IDH1/2 mutations occur in enchondromas and chondrosarcomas in patients with the non-hereditary enchondromatosis syndromes Ollier disease and Maffucci syndrome and in sporadic tumors. IDH1/2 mutations result in excess production of the oncometabolite (D)-2-hydroxyglutarate...
January 16, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29339751/jmjc-domain-proteins-modulate-circadian-behaviors-and-sleep-in-drosophila
#3
Nevine A Shalaby, Jorge H Pinzon, Anjana S Narayanan, Eugene Jennifer Jin, Morgan P Ritz, Rachel J Dove, Heike Wolfenberg, Aylin R Rodan, Michael Buszczak, Adrian Rothenfluh
Jumonji (JmjC) domain proteins are known regulators of gene expression and chromatin organization by way of histone demethylation. Chromatin modification and remodeling provides a means to modulate the activity of large numbers of genes, but the importance of this class of predicted histone-modifying enzymes for different aspects of post-developmental processes remains poorly understood. Here we test the function of all 11 non-lethal members in the regulation of circadian rhythms and sleep. We find loss of every Drosophila JmjC gene affects different aspects of circadian behavior and sleep in a specific manner...
January 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29336484/epigenetic-regulation-of-megakaryocytic-and-erythroid-differentiation-by-phf2-histone-demethylase
#4
Jichun Yang, Jing Ma, Yu Xiong, Yanlin Wang, Kaiyue Jin, Wenjun Xia, Qing Chen, Jianbo Huang, Jin Zhang, Nan Jiang, Shayi Jiang, Duan Ma
Plant homeodomain finger 2 (PHF2) is a JmjC family histone demethylase that demethylates H3K9me2, a repressive gene marker. PHF2 was found to play a role in the differentiation of several tissue types such as osteoblast and adipocyte differentiation. We report here that PHF2 plays a role in the epigenetic regulation of megakaryocytic (MK) and erythroid differentiation. We investigated PHF2 expression during MK and erythroid differentiation in K562 and human CD34+ progenitor (hCD34+ ) cells. Our data demonstrate that PHF2 expression is down-regulated during megakaryopoiesis and erythropoiesis...
January 16, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29324315/histone-demethylase-kdm5a-inhibits-glioma-cells-migration-and-invasion-by-down-regulating-zeb1
#5
Bin Dai, Hui Huang, Feng Guan, Guangtong Zhu, Zhiyong Xiao, Beibei Mao, Haiyang Su, Zhiqiang Hu
Malignant gliomas are highly lethal cancers worldwide as tumor cells infiltrate to healthy brain tissue invariably. Histone demethylase KDM5A as an oncogene or tumor suppressor in cancer still has been controversial. KDM5A may have a different function in different type cancer cells. However, the specific roles of KDM5A in the progression of glioma remain undiscovered. In this study, we found that compared with primary glioma, metastasis glioma had low KDM5A levels. Besides, lower KDM5A levels were linked to poor survival in glioma cancer patients, indicating that KDM5A is a new prognostic marker for glioma cancer...
January 8, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29318497/epigenetic-mechanism-of-survivin-dysregulation-in-human-cancer
#6
REVIEW
Hui Lyu, Jingcao Huang, Zhimin He, Bolin Liu
Survivin (coding gene BIRC5) is a dual functional protein acting as a critical inhibitor of apoptosis (IAP) and key regulator of cell cycle progression. It is usually produced in embryonic tissues during development and undetectable in most adult tissues. Overexpression of Survivin frequently occurs in various human cancers and increased Survivin correlates with poor clinic outcome, tumor recurrence, and therapeutic resistance. Because of its selective expression in tumor, but not normal tissues, Survivin has been recognized as an attractive target for cancer treatment...
January 4, 2018: Science China. Life Sciences
https://www.readbyqxmd.com/read/29317619/phf8-histone-demethylase-deficiency-causes-cognitive-impairments-through-the-mtor-pathway
#7
Xuemei Chen, Shuai Wang, Ying Zhou, Yanfei Han, Shengtian Li, Qing Xu, Longyong Xu, Ziqi Zhu, Youming Deng, Lu Yu, Lulu Song, Adele Pin Chen, Juan Song, Eiki Takahashi, Guang He, Lin He, Weidong Li, Charlie Degui Chen
Epigenomic abnormalities caused by genetic mutation in epigenetic regulators can result in neurodevelopmental disorders, deficiency in neural plasticity and mental retardation. As a histone demethylase, plant homeodomain finger protein 8 (Phf8) is a candidate gene for syndromal and non-specific forms of X-chromosome-linked intellectual disability (XLID). Here we report that Phf8 knockout mice displayed impaired learning and memory, and impaired hippocampal long-term potentiation (LTP) without gross morphological defects...
January 9, 2018: Nature Communications
https://www.readbyqxmd.com/read/29301935/-inhibition-of-histone-h3k27-demethylase-selectively-modulates-inflammatory-phenotypes-of-natural-killer-cells
#8
Adam Cribbs, Edward S Hookway, Graham Wells, Morten Lindow, Susanna Obad, Henrik Oerum, Rab K Prinjha, Nick Athanasou, Aneka Sowman, Martin Philpott, Henry Penn, Kalle Soderstrom, Marc Feldmann, Udo Oppermann
Natural killer (NK) cells are innate lymphocytes, important in immune surveillance and elimination of stressed, transformed, or virus-infected cells. They critically shape the inflammatory cytokine environment to orchestrate interactions of cells of the innate and adaptive immune systems. Some studies have reported that NK cell activation and cytokine secretion are controlled epigenetically, but have yielded only limited insight into the mechanisms. Using chemical screening with small-molecule inhibitors of chromatin methylation and acetylation, further validated by knockdown approaches, we here identified Jumonji-type histone H3K27 demethylases as key regulators of cytokine production in human NK cell subsets...
January 4, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29286868/elongator-promotes-germination-and-early-post-germination-growth
#9
Magdalena Wołoszyńska, Olimpia Gagliardi, Filip Vandenbussche, Mieke Van Lijsebettens
The Elongator complex interacts with RNA polymerase II and via histone acetylation and DNA demethylation facilitates epigenetically the transcription of genes involved in diverse processes in plants, including growth, development, and immune response. Recently, we have shown that the Elongator complex promotes hypocotyl elongation and photomorphogenesis in Arabidopsis thaliana by regulating the photomorphogenesis and growth-related gene network that converges on genes implicated in cell wall biogenesis and hormone signaling...
December 29, 2017: Plant Signaling & Behavior
https://www.readbyqxmd.com/read/29286640/separation-of-methylated-histone-peptides-via-host-assisted-capillary-electrophoresis
#10
Jiwon Lee, Lizeth Perez, Yang Liu, Hua Wang, Richard J Hooley, Wenwan Zhong
Lysine methylation in protein is one important epigenetic mechanism that regulates diverse biological processes, but is chal-lenging to study due to the large variability in methylation levels and sites. Here we show that supramolecular hosts such as calixarenes and cucurbiturils can be applied in the background electrolyte (BGE) of capillary electrophoresis (CE) for highly effective separation of post-translationally methylated histone peptides. The molecular recognition event causes a shift in the electrophoretic mobility of the peptide, allowing affinity measurement for binding between the synthetic receptor and various methylated lysine species...
December 29, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/29286617/genistein-and-trichostatin-a-induction-of-estrogen-receptor-alpha-gene-expression-apoptosis-and-cell-growth-inhibition-in-hepatocellular-carcinoma-hepg-2-cells
#11
Masumeh Sanaei, Fraidoon Kavoosi, Habibeh Salehi
Epigenetic changes such as DNA methylation and histone acetylation play important roles in determining gene expression. Hypermethylation of CpG islands of the promoter region of tumor suppressor genes can greatly influence carcinogenesis through transcriptional silencing. Acetylation of lysine in histone tails causes relaxation of chromatin, which facilitates gene transcription, while deacetylation is associated with condensed chromatin resulting in gene silencing. DNA demethylating agents such as genistein (GE) and histone deacetylase inhibitors (HDACIs) such as trichostatin A (TSA) may strongly reactivate silenced genes and exposure to these two agents in combination is reported to enhance estrogen receptor alpha (ERα) reactivation and induction of apoptosis...
December 29, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/29281729/histone-demethylase-lsd1-restricts-influenza-a-virus-infection-by-erasing-ifitm3-k88-monomethylation
#12
Jiaoyu Shan, Binbin Zhao, Zhao Shan, Jia Nie, Rong Deng, Rui Xiong, Andy Tsun, Weiqi Pan, Hanzhi Zhao, Ling Chen, Ying Jin, Zhikang Qian, Kawing Lui, Rui Liang, Dan Li, Bing Sun, Dimitri Lavillette, Ke Xu, Bin Li
The histone demethylase LSD1 has been known as a key transcriptional coactivator for DNA viruses such as herpes virus. Inhibition of LSD1 was found to block viral genome transcription and lytic replication of DNA viruses. However, RNA virus genomes do not rely on chromatin structure and histone association, and the role of demethylase activity of LSD1 in RNA virus infections is not anticipated. Here, we identify that, contrary to its role in enhancing DNA virus replication, LSD1 limits RNA virus replication by demethylating and activating IFITM3 which is a host restriction factor for many RNA viruses...
December 27, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/29281014/systematic-genetic-interaction-studies-identify-histone-demethylase-utx-as-potential-target-for-ameliorating-huntington-s-disease
#13
Wan Song, Nóra Zsindely, Anikó Faragó, J Lawrence Marsh, László Bodai
Huntington's Disease (HD) is a dominantly inherited neurodegenerative disease caused by alterations in the huntingtin gene (htt). Transcriptional dysregulation is an early event in HD progression. Protein acetylation and methylation particularly on histones regulates chromatin structure thereby preventing or facilitating transcription. Although protein acetylation has been found to affect HD symptoms, little is known about the potential role of protein methylation in HD pathology. In recent years, a series of proteins have been described that are responsible for methylating and demethylating histones as well as other proteins...
December 21, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/29262320/the-arginine-methyltransferase-prmt6-regulates-dna-methylation-and-contributes-to-global-dna-hypomethylation-in-cancer
#14
Nicolas Veland, Swanand Hardikar, Yi Zhong, Sitaram Gayatri, Jiameng Dan, Brian D Strahl, Scott B Rothbart, Mark T Bedford, Taiping Chen
DNA methylation plays crucial roles in chromatin structure and gene expression. Aberrant DNA methylation patterns, including global hypomethylation and regional hypermethylation, are associated with cancer and implicated in oncogenic events. How DNA methylation is regulated in developmental and cellular processes and dysregulated in cancer is poorly understood. Here, we show that PRMT6, a protein arginine methyltransferase responsible for asymmetric dimethylation of histone H3 arginine 2 (H3R2me2a), negatively regulates DNA methylation and that PRMT6 upregulation contributes to global DNA hypomethylation in cancer...
December 19, 2017: Cell Reports
https://www.readbyqxmd.com/read/29259864/an-up-date-on-epigenetic-and-molecular-markers-in-testicular-germ-cell-tumors
#15
Paolo Chieffi
Testicular germ cell tumor (TGCT) is the most common solid malignancy occurring in young men between 20 and 34 years of age, and its incidence has increased significantly over the last decades. Clinically several types of immunohistochemical markers are useful and sensitive. These new biomarkers are genes expressed in primordial germ cells/gonocytes and embryonic pluripotency-related cells but not in normal adult germ cells and they include OCT3/4, HMGA1 and 2, NANOG, SOX2, and LIN28. Gene expression in TGCT is regulated, at least in part, by DNA and histone modifications, and the epigenetic profile of these tumours is characterised by genome-wide demethylation...
November 2017: Intractable & Rare Diseases Research
https://www.readbyqxmd.com/read/29247011/histone-demethylase-activity-of-utx-is-essential-for-viability-and-regulation-of%C3%A2-hox-gene-expression-in%C3%A2-drosophila
#16
Ömer Copur, Jürg Müller
The trimethylation of histone H3 at lysine 27 (H3K27me3) by Polycomb Repressive Complex 2 (PRC2) is essential for repression of Polycomb target genes. The role of enzymatic demethylation of H3K27me3 by the KDM6-family demethylases Utx, Uty and JmjD3 is however less clear. Studies in both mice and worms led to the proposal that KDM6 proteins but not their H3K27me3 demethylase activity is critical for normal development. Here, we investigated the requirement of the demethylase activity of the single KDM6 family member Utx in Drosophila We generated Drosophila expressing full-length but catalytic inactive Utx protein and found that these mutants show the same phenotypes like animals lacking Utx protein...
December 15, 2017: Genetics
https://www.readbyqxmd.com/read/29246768/pip2-epigenetically-represses-rrna-genes-transcription-interacting-with-phf8
#17
Ulicna Livia, Kalendova Alzbeta, Kalasova Ilona, Vacik Tomas, Hozak Pavel
Phosphoinositides are present in the plasma membrane, cytoplasm and inside the cell nucleus. Here we identify phosphatidylinositol-4,5-bisphosphate (PIP2) as a regulator of rRNA genes transcription at the epigenetic level. We show that PIP2 directly interacts with histone lysine demethylase PHF8 (PHD finger protein 8) and represses demethylation of H3K9me2 through this interaction. We identify the C-terminal K/R-rich motif as PIP2-binding site within PHF8, and address the function of this PIP2-PHF8 complex...
December 12, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29245970/calcitriol-induces-cell-senescence-of-kidney-cancer-through-jmjd3-mediated-histone-demethylation
#18
Yongqing Shen, Dan Yu, Pan Qi, Xuliang Wang, Xiaoqiang Guo, Aili Zhang
Calcitriol, also known as 1,25-dihydroxyvitamin D3 (1,25(OH)2VD3), is a biologically active form of vitamin D and has a wide range of anticancer activity against various cancer cell lines. However, the mechanism of calcitriol remains to be further studied. In this study, the biological effect and epigenetic regulation of calcitriol on kidney cancer cells were investigated. Calcitriol can significantly inhibit cell proliferation of kidney cancer cell lines 786-O (P<0.05). Calcitriol also induced cell apoptosis and senescence of 786-O and ACHN (P<0...
November 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/29224413/low-hox-gene-expression-in-pml-rar%C3%AE-positive-leukemia-results-from-suppressed-histone-demethylation
#19
Kateřina Rejlová, Alena Musilová, Karolina Škvárová Kramarzová, Markéta Žaliová, Karel Fišer, Meritxell Alberich-Jorda, Jan Trka, Júlia Starková
Homeobox (HOX) genes are frequently dysregulated in leukemia. Previous studies have shown that aberrant HOX gene expression accompanies leukemogenesis and affects disease progression and leukemia patient survival. Patients with acute myeloid leukemia (AML) bearing PML-RARα fusion gene has distinct HOX gene signature in comparison to other subtypes of AML patients although the mechanism of transcription regulation is not completely understood. We previously found an association between the mRNA levels of HOX genes and those of the histone demethylases JMJD3 and UTX in PML-RARα- positive leukemia patients...
December 11, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/29220567/the-structural-basis-of-the-histone-demethylase-kdm6b-histone-3-lysine-27-specificity
#20
Sarah Elizabeth Jones, Lars Olsen, Michael Gajhede
KDM subfamily 6 enzymes KDM6A and KDM6B specifically catalyse demethylation of di-/tri-methylated lysine on Histone 3 lysine 27 (H3K27me3/2) and play an important role in repression of developmental genes. Despite identical amino acid sequence in the immediate surroundings of H3K9me3/2 (ARKS) the enzymes do not catalyse demethylation of this general marker of repression. In order to address this question for KDM6B we used computational methods to identify H3(17-33) derived peptides with improved binding affinity, that would enable co-crystallization with the catalytic core of human KDM6B (ccKDM6B)...
December 8, 2017: Biochemistry
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