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https://www.readbyqxmd.com/read/29156705/upregulation-of-cd11b-and-cd86-through-lsd1-inhibition-promotes-myeloid-differentiation-and-suppresses-cell-proliferation-in-human-monocytic-leukemia-cells
#1
Jianwu Fang, Haiyan Ying, Ting Mao, Yanjia Fang, Yuan Lu, He Wang, Irene Zang, Zhaofu Wang, Ying Lin, Mengxi Zhao, Xiao Luo, Zongyao Wang, Yan Zhang, Chao Zhang, Wei Xiao, Yan Wang, Wei Tan, Zhui Chen, Chris Lu, Peter Atadja, En Li, Kehao Zhao, Jianfeng Liu, Justin Gu
LSD1 (Lysine Specific Demethylase1)/KDM1A (Lysine Demethylase 1A), a flavin adenine dinucleotide (FAD)-dependent histone H3K4/K9 demethylase, sustains oncogenic potential of leukemia stem cells in primary human leukemia cells. However, the pro-differentiation and anti-proliferation effects of LSD1 inhibition in acute myeloid leukemia (AML) are not yet fully understood. Here, we report that small hairpin RNA (shRNA) mediated LSD1 inhibition causes a remarkable transcriptional activation of myeloid lineage marker genes (CD11b/ITGAM and CD86), reduction of cell proliferation and decrease of clonogenic ability of human AML cells...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29150847/chronic-sun-exposure-is-associated-with-distinct-histone-acetylation-changes-in-human-skin
#2
S Ding, J Chen, Q Zeng, J Lu, L Tan, A Guo, J Kang, S Yang, Y Xiang, C Zuo, J Huang
BACKGROUND: Photoaging is attributed to continuous sunlight or artificial UV exposure and manifests the clinical and histological changes of skin. Epigenetic changes have been found to be involved in the pathogenesis of photoaging. However, the underlying mechanisms are unclear. OBJECTIVES: To analyse histone modification patterns in sun-exposed and non-exposed skins, and identify the abnormally histone modified-genes related to photoaging. METHODS: Skin biopsies were collected both from the outer forearm (sun-exposed area) and the buttock (sun-protected area) in 20 healthy middle-aged female volunteers...
November 18, 2017: British Journal of Dermatology
https://www.readbyqxmd.com/read/29148585/arsenite-downregulates-h3k4-trimethylation-and-h3k9-dimethylation-during-transformation-of-human-bronchial-epithelial-cells
#3
Wei Tu, Yin Liu, Chengfeng Xie, Xue Zhou
Arsenic is an established human carcinogen but with weak mutagenic activity. The mechanisms of arsenic-induced carcinogenesis are not well understood. In the present study, we investigated the role of histone methylation in transformation of human bronchial epithelial (BEAS-2B) cells. After 16 weeks' exposure, cells were transformed by 0.1, 0.5 and 1 μm arsenite. Global trimethylated H3K4 (H3K4me3) was decreased by 0.1 μm arsenite at 12 weeks, and 0.5 and 1 μm arsenite at 8, 12 and 16 weeks, which could be attributed to reduced histone methyltransferase activities, increased histone demethylase (HDM) activities as well as increased protein levels of H3K4 demethylase KDM5A...
November 17, 2017: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/29142068/pharmacologic-inhibition-of-the-menin-mll-interaction-leads-to-transcriptional-repression-of-peg10-and-blocks-hepatocellular-carcinoma
#4
Katarzyna Kempinska, Bhavna Malik, Dmitry Borkin, Szymon Klossowski, Shirish Shukla, Hongzhi Miao, Jingya Wang, Tomasz Cierpicki, Jolanta Grembecka
Hepatocellular carcinoma (HCC) accounts for ~85% of malignant liver tumors and results in 600,000 deaths each year, emphasizing the need for new therapies. Upregulation of menin was reported in HCC patients and high levels of menin correlate with poor patient prognosis. The protein-protein interaction between menin and histone methyltransferase Mixed Lineage Leukemia 1 (MLL1) plays an important role in the development of HCC, implying that pharmacologic inhibition of this interaction could lead to new therapeutic strategy for the HCC patients...
November 15, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29138553/the-protective-effect-of-prmt6-overexpression-on-cigarette-smoke-extract-induced-murine-emphysema-model
#5
Xue He, Tiao Li, Naixin Kang, Huihui Zeng, Siying Ren, Dandan Zong, Jinhua Li, Shan Cai, Ping Chen, Yan Chen
Background: Cigarette smoke exposure is the most common risk factor for emphysema, which is one of the major pathologies of COPD. Protein arginine methyltransferase 6 (PRMT6) is a nuclear enzyme that specially catalyzes dimethylation of R2 in histone H3 (H3R2me2a). H3R2me2a prevents trimethylation of H3K4 (H3K4me3), which is located in the transcription start sites of genes in mammalian genomes. We attempted to determine the expression of PRMT6 in human samples, and investigate whether the upregulation of PRMT6 expression can attenuate the development of cigarette smoke extract (CSE)-induced emphysema...
2017: International Journal of Chronic Obstructive Pulmonary Disease
https://www.readbyqxmd.com/read/29137396/tgfbr-idh1-cav1-axis-promotes-tgf-%C3%AE-signalling-in-cancer-associated-fibroblast
#6
Xiaodan Hou, Jieying Zhang, Yongbin Wang, Wujun Xiong, Jun Mi
TGF-β signalling plays an important role in fibroblasts activation and tumour progression. Here, we report that the TGFBR-IDH1-Cav1 axis promotes TGF- β signalling in fibroblasts. Our data demonstrated that IDH1 was downregulated by TGF-β signalling in fibroblasts, and downregulation of IDH1 increased cellular concentration of α-ketoglutarate (α-KG) by accelerating glutamine metabolization. Interestingly, α-KG suppressed Cav1 expression through reducing the trimethylation of histone H3K4. Furthermore, Cav1 downregulation inhibited TGFBR protein degradation...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29137219/functional-characterization-of-lysine-specific-demethylase-2-lsd2-kdm1b-in-breast-cancer-progression
#7
Lin Chen, Shauna N Vasilatos, Ye Qin, Tiffany A Katz, Chunyu Cao, Hao Wu, Nilgun Tasdemir, Kevin M Levine, Steffi Oesterreich, Nancy E Davidson, Yi Huang
Flavin-dependent histone demethylases govern histone H3K4 methylation and act as important chromatin modulators that are extensively involved in regulation of DNA replication, gene transcription, DNA repair, and heterochromatin gene silencing. While the activities of lysine-specific demethylase 1 (LSD1/KDM1A) in facilitating breast cancer progression have been well characterized, the roles of its homolog LSD2 (KDM1B) in breast oncogenesis are relatively less understood. In this study, we showed that LSD2 protein level was significantly elevated in malignant breast cell lines compared with normal breast epithelial cell line...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29133016/dynamic-transcriptional-control-of-macrophage-mirna-signature-via-inflammation-responsive-enhancers-revealed-using-a-combination-of-next-generation-sequencing-based-approaches
#8
Zsolt Czimmerer, Attila Horvath, Bence Daniel, Gergely Nagy, Ixchelt Cuaranta-Monroy, Mate Kiss, Zsuzsanna Kolostyak, Szilard Poliska, Laszlo Steiner, Nikolas Giannakis, Tamas Varga, Laszlo Nagy
MicroRNAs are important components of the post-transcriptional fine-tuning of macrophage gene expression in physiological and pathological conditions. However, the mechanistic underpinnings and the cis-acting genomic factors of how macrophage polarizing signals induce miRNA expression changes are not well characterized. Therefore, we systematically evaluated the transcriptional basis underlying the inflammation-mediated regulation of macrophage microRNome using the combination of different next generation sequencing datasets...
November 10, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29130522/rhoj-promotes-hypoxia-induced-endothelial-to-mesenchymal-transition-by-activating-wdr5-expression
#9
Li Liu, Junliang Chen, Lina Sun
Endothelial-to-mesenchymal transition (EndMT) contributes to the pathogenesis of a host of human diseases. RhoJ, a small G protein, is abundantly expressed in endothelial cells. In the present study we investigated the potential role RhoJ plays in EndMT. We report that RhoJ depletion by small interfering RNA attenuated hypoxia induced EndMT in both immortalized endothelial cells and human primary microvascular endothelial cells. RhoJ knockdown blocked the recruitment of TWIST and SNAIL, two transcriptional repressors, to the promoter region of VE-CADHERIN, a prominent endothelial marker...
November 11, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29129639/determinants-of-histone-h3k4-methylation-patterns
#10
Luis M Soares, P Cody He, Yujin Chun, Hyunsuk Suh, TaeSoo Kim, Stephen Buratowski
Various factors differentially recognize trimethylated histone H3 lysine 4 (H3K4me3) near promoters, H3K4me2 just downstream, and promoter-distal H3K4me1 to modulate gene expression. This methylation "gradient" is thought to result from preferential binding of the H3K4 methyltransferase Set1/complex associated with Set1 (COMPASS) to promoter-proximal RNA polymerase II. However, other studies have suggested that location-specific cues allosterically activate Set1. Chromatin immunoprecipitation sequencing (ChIP-seq) experiments show that H3K4 methylation patterns on active genes are not universal or fixed and change in response to both transcription elongation rate and frequency as well as reduced COMPASS activity...
November 16, 2017: Molecular Cell
https://www.readbyqxmd.com/read/29125890/up-regulated-wdr5-promotes-gastric-cancer-formation-by-induced-cyclin-d1-expression
#11
Wei Sun, Fuchao Guo, Mingkai Liu
Gastric cancer (GC) is the fourth common cancer and second leading cause of cancer-related mortality in the world. WD repeat domain 5 (WDR5) has been identified that its functions as an important role in various biological functions through the epigenetic regulation of gene transcription. However, the oncogenic effect of WDR5 in gastric cancer remains largely unknown. In this study, we investigated the role of WDR5 in gastric cancer genesis. We found that WDR5 expression is increased in gastric cancer patients...
November 10, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29113269/the-expression-and-significance-of-histone-lysine-methylation-in-endometrial-cancer
#12
Qing Li, Nan Jia, Xiang Tao, Keqin Hua, Weiwei Feng
Histone modifications of lysine residues have been implicated as having diagnostic and/or prognostic significance in numerous types of cancer. In the present study, the significance of the histone H3 methylation of lysine 4 (H3K4) and lysine 27 (H3K27) were investigated in endometrial cancer. Specifically, immunohistochemical analysis was used to detect the cellular expression levels of H3K27 trimethylation (H3K27me3), H3K4 trimethylation (H3K4me3) and H3K4 dimethylation (H3K4me2) in glandular epithelial tissues and stromal tissues...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/29109331/mkl1-mediates-tnf-%C3%AE-induced-pro-inflammatory-transcription-by-bridging-the-crosstalk-between-brg1-and-wdr5
#13
Wenping Xu, Quanyi Zhao, Min Wu, Mingming Fang, Yong Xu
Tumor necrosis factor alpha (TNF-α) is a cytokine that can potently stimulate the synthesis of a range of pro-inflammatory mediators in macrophages. The underlying epigenetic mechanism, however, is underexplored. Here we report that the transcriptional modulator megakaryocytic leukemia 1 (MKL1) is associated with a histone H3K4 methyltransferase activity. Re-ChIP assay suggests that MKL1 interacts with and recruits WDR5, a component of the COMPASS complex responsible for H3K4 methylation, to the promoter regions of pro-inflammatory genes in macrophages treated with TNF-α...
November 1, 2017: Journal of Biomedical Research
https://www.readbyqxmd.com/read/29089422/a-cryptic-tudor-domain-links-brwd2-phip-to-compass-mediated-histone-h3k4-methylation
#14
Marc A J Morgan, Ryan A Rickels, Clayton K Collings, Xiaolin He, Kaixiang Cao, Hans-Martin Herz, Kira A Cozzolino, Nebiyu A Abshiru, Stacy A Marshall, Emily J Rendleman, Christie C Sze, Andrea Piunti, Neil L Kelleher, Jeffrey N Savas, Ali Shilatifard
Histone H3 Lys4 (H3K4) methylation is a chromatin feature enriched at gene cis-regulatory sequences such as promoters and enhancers. Here we identify an evolutionarily conserved factor, BRWD2/PHIP, which colocalizes with histone H3K4 methylation genome-wide in human cells, mouse embryonic stem cells, and Drosophila Biochemical analysis of BRWD2 demonstrated an association with the Cullin-4-RING ubiquitin E3 ligase-4 (CRL4) complex, nucleosomes, and chromatin remodelers. BRWD2/PHIP binds directly to H3K4 methylation through a previously unidentified chromatin-binding module related to Royal Family Tudor domains, which we named the CryptoTudor domain...
October 1, 2017: Genes & Development
https://www.readbyqxmd.com/read/29082293/reprogram-murine-epiblast-stem-cells-by-epigenetic-inhibitors
#15
Hui Zhang, Yali Dou
Pluripotent stem cells in the naïve state are highly useful in regenerative medicine and tissue engineering. A robust reprogramming of the primed murine Epiblast Stem Cells (EpiSCs) to naïve pluripotency is feasible via chemical-only approach. This protocol described a method to reprogram murine EpiSCs by MM-401 treatment, which blocks histone H3K4 methylation by MLL1/KMT2A.
March 5, 2017: Bio-protocol
https://www.readbyqxmd.com/read/29071121/binding-to-rna-regulates-set1-function
#16
Pierre Luciano, Jongcheol Jeon, Abdessamad El-Kaoutari, Drice Challal, Amandine Bonnet, Mara Barucco, Tito Candelli, Frederic Jourquin, Pascale Lesage, Jaehoon Kim, Domenico Libri, Vincent Géli
The Set1 family of histone H3 lysine 4 (H3K4) methyltransferases is highly conserved from yeast to human. Here we show that the Set1 complex (Set1C) directly binds RNA in vitro through the regions that comprise the double RNA recognition motifs (dRRM) and N-SET domain within Set1 and its subunit Spp1. To investigate the functional relevance of RNA binding, we performed UV RNA crosslinking (CRAC) for Set1 and RNA polymerase II in parallel with ChIP-seq experiments. Set1 binds nascent transcripts through its dRRM...
2017: Cell Discovery
https://www.readbyqxmd.com/read/29066473/repression-of-middle-sporulation-genes-in-saccharomyces-cerevisiae-by-the-sum1-rfm1-hst1-complex-is-maintained-by-set1-and-h3k4-methylation
#17
Deepika Jaiswal, Meagan Jezek, Jeremiah Quijote, Joanna Lum, Grace Choi, Rushmie Kulkarni, DoHwan Park, Erin M Green
The conserved yeast histone methyltransferase Set1 targets H3 lysine 4 (H3K4) for mono-, di- and tri-methylation and is linked to active transcription due to the euchromatic distribution of these methyl marks and the recruitment of Set1 during transcription. However, loss of Set1 results in increased expression of multiple classes of genes, including genes adjacent to telomeres and middle sporulation genes, which are repressed under normal growth conditions because they function in meiotic progression and spore formation...
November 4, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/29061907/deubiquitllating-enzyme-otu5-contributes-to-dna-methylation-patterns-and-is-critical-for-phosphate-nutrition-signals
#18
Ming-Ren Yen, Der-Fen Suen, Fei-Man Hsu, Yi-Hsiu Tsai, Hongyong Fu, Wolfgang Schmidt, Pao-Yang Chen
Phosphate (Pi) starvation induces a suite of adaptive responses aimed at recalibrating cellular Pi homeostasis. Plants harboring a mutation in OVARIAN TUMOR DOMAIN-CONTAINING DEUBIQUITILATING ENZYME5 (OTU5) showed altered DNA methylation of root hair-related genes and altered Pi-responsive root traits. Unlike the wild type, homozygous otu5 mutants did not respond to Pi starvation by increased lateral root formation and increased root hair length, but formed very short root hairs when grown on low Pi media. Under Pi-replete conditions, otu5 plants developed more root hairs than the wild type due to attenuated primary root growth, a phenotype which resembled that of Pi-deficient plants...
October 23, 2017: Plant Physiology
https://www.readbyqxmd.com/read/29059406/dynamic-site-specific-recruitment-of-rbp2-by-pocket-protein-p130-modulates-h3k4-methylation-on-e2f-responsive-promoters
#19
Zaffer Ullah Zargar, Mallikharjuna Rao Kimidi, Shweta Tyagi
The Histone 3 lysine 4 methylation (H3K4me3) mark closely correlates with active transcription. E2F-responsive promoters display dynamic changes in H3K4 methylation during the course of cell cycle progression. However, how and when these marks are reset, is not known. Here we show that the retinoblastoma binding protein RBP2/KDM5A, capable of removing tri-methylation marks on H3K4, associates with the E2F4 transcription factor via the pocket protein-p130-in a cell-cycle-stage specific manner. The association of RBP2 with p130 is LxCxE motif dependent...
October 20, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29038917/chromatin-associated-regulation-of-sorbitol-synthesis-in-flower-buds-of-peach
#20
Alba Lloret, Amparo Martínez-Fuentes, Manuel Agustí, María Luisa Badenes, Gabino Ríos
PpeS6PDH gene is postulated to mediate sorbitol synthesis in flower buds of peach concomitantly with specific chromatin modifications. Perennial plants have evolved an adaptive mechanism involving protection of meristems within specialized structures named buds in order to survive low temperatures and water deprivation during winter. A seasonal period of dormancy further improves tolerance of buds to environmental stresses through specific mechanisms poorly known at the molecular level. We have shown that peach PpeS6PDH gene is down-regulated in flower buds after dormancy release, concomitantly with changes in the methylation level at specific lysine residues of histone H3 (H3K27 and H3K4) in the chromatin around the translation start site of the gene...
October 16, 2017: Plant Molecular Biology
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