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https://www.readbyqxmd.com/read/28067305/gomisin-n-inhibits-adipogenesis-and-prevents-high-fat-diet-induced-obesity
#1
Min-Kyung Jang, Ye-Rang Yun, Ji-Hyun Kim, Mi-Hee Park, Myeong Ho Jung
Gomisin N (GN) is a physiological lignan derived from Schisandra chinensis. In the present study, we investigated the inhibitory effects of GN on differentiation of 3T3-L1 preadipocytes and the anti-obesity effects of GN in high-fat diet (HFD)-induced obese mice. Incubation with GN significantly inhibited the differentiation of 3T3-L1 preadipocytes in a dose-dependent manner. This inhibitory effect primarily occurred at an early adipogenic stage through impairment of mitotic clonal expansion (MCE) caused by cell cycle arrest at the G1/S phase transition...
January 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28050603/new-open-conformation-of-smyd3-implicates-conformational-selection-and-allostery
#2
Nicholas Spellmon, Xiaonan Sun, Wen Xue, Joshua Holcomb, Srinivas Chakravarthy, Weifeng Shang, Brian Edwards, Nualpun Sirinupong, Chunying Li, Zhe Yang
SMYD3 plays a key role in cancer cell viability, adhesion, migration and invasion. SMYD3 promotes formation of inducible regulatory T cells and is involved in reducing autoimmunity. However, the nearly "closed" substrate-binding site and poor in vitro H3K4 methyltransferase activity have obscured further understanding of this oncogenically related protein. Here we reveal that SMYD3 can adopt an "open" conformation using molecular dynamics simulation and small-angle X-ray scattering. This ligand-binding-capable open state is related to the crystal structure-like closed state by a striking clamshell-like inter-lobe dynamics...
2017: AIMS Biophysics
https://www.readbyqxmd.com/read/28049706/coordination-of-cell-cycle-progression-and-mitotic-spindle-assembly-involves-histone-h3-lysine-4-methylation-by-set1-compass
#3
Traude H Beilharz, Paul F Harrison, Douglas Maya Miles, Michael Ming See, Uyen Minh Merry Le, Ming Kalanon, Melissa Jane Curtis, Qambar Hasan, Julie Saksouk, Thanasis Margaritis, Frank Holstege, Vincent Geli, Bernhard Dichtl
Methylation of histone H3 lysine 4 (H3K4) by Set1 complex/COMPASS is a hallmark of eukaryotic chromatin, but it remains poorly understood how this post-translational modification contributes to the regulation of biological processes like the cell cycle. Here, we report a H3K4 methylation-dependent pathway in Saccharomyces cerevisiae that governs toxicity toward benomyl, a microtubule destabilizing drug. Benomyl-sensitive growth of wild-type cells required mono- and dimethylation of H3K4 and Pho23, a PHD-containing subunit of the Rpd3L complex...
January 2017: Genetics
https://www.readbyqxmd.com/read/28045584/epigenetic-countermarks-in-mitotic-chromosome-condensation
#4
Karel H M van Wely, Carmen Mora Gallardo, Kendra R Vann, Tatiana G Kutateladze
Mitosis in metazoans is characterized by abundant phosphorylation of histone H3 and involves the recruitment of condensin complexes to chromatin. The relationship between the two phenomena and their respective contributions to chromosome condensation in vivo remain poorly understood. Recent studies have shown that H3T3 phosphorylation decreases binding of histone readers to methylated H3K4 in vitro and is essential to displace the corresponding proteins from mitotic chromatin in vivo. Together with previous observations, these data provide further evidence for a role of mitotic histone H3 phosphorylation in blocking transcriptional programs or preserving the 'memory' PTMs...
January 3, 2017: Nucleus
https://www.readbyqxmd.com/read/28033672/txnip-mediates-the-differential-responses-of-a549-cells-to-sodium-butyrate-and-sodium-4-phenylbutyrate-treatment
#5
Xuefang Jin, Nana Wu, Juji Dai, Qiuxia Li, XiaoQiang Xiao
Sodium butyrate (NaBu) and sodium 4-phenylbutyrate (4PBA) have promising futures in cancer treatment; however, their underlying molecular mechanisms are not clearly understood. Here, we show A549 cell death induced by NaBu and 4PBA are not the same. NaBu treatment induces a significantly higher level of A549 cell death than 4PBA. A gene expression microarray identified more than 5000 transcripts that were altered (>1.5-fold) in NaBu-treated A549 cells, but fewer than 2000 transcripts that were altered in 4PBA...
December 29, 2016: Cancer Medicine
https://www.readbyqxmd.com/read/28027934/histone-modifications-in-fasn-modulated-by-sterol-regulatory-element-binding-protein-1c-and-carbohydrate-responsive-element-binding-protein-under-insulin-stimulation-are-related-to-nafld
#6
Wei Shen, Xuan Du, Can Cai, Jialing Yao, Youping Zhou, Huihong Yu
Non-alcoholic fatty liver disease (NAFLD) and its causal factors of hepatic insulin resistance (IR) and type 2 diabetes are rapidly growing worldwide. Developing new therapeutic methods for these conditions requires a comprehensive understanding between hepatic lipid metabolism and IR. Sterol regulatory element-binding transcription factor 1c (SREBP-1c) and carbohydrate responsive-element binding protein (ChREBP) are the major regulators of fatty acid synthase (FASN), a key enzyme of de novo fatty acid synthesis...
December 24, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28027012/dynamic-chromatin-regulation-at-notch-target-genes
#7
Benedetto Daniele Giaimo, Franz Oswald, Tilman Borggrefe
RBPJ is the central transcription factor that controls the Notch-dependent transcriptional response by coordinating repressing histone H3K27 deacetylation and activating histone H3K4 methylation. Here, we discuss the molecular mechanisms how RBPJ interacts with opposing NCoR/HDAC-corepressing or KMT2D/UTX-coactivating complexes and how this is controlled by phosphorylation of chromatin modifiers.
December 27, 2016: Transcription
https://www.readbyqxmd.com/read/28013028/h3k4-methyltransferase-activity-is-required-for-mll4-protein-stability
#8
Younghoon Jang, Chaochen Wang, Lenan Zhuang, Chengyu Liu, Kai Ge
Transcriptional enhancers play a key role in cell type-specific gene expression and cell fate transition. Enhancers are marked by histone H3K4 mono- and di-methylation (H3K4me1/2). The tumor suppressor MLL4 (KMT2D) is a major enhancer H3K4 mono- and di-methyltransferase with a partial functional redundancy with MLL3 (KMT2C). However, the functional role of MLL4 enzymatic activity remains elusive. To address this issue, we have generated MLL4 enzyme-dead knock-in (KI) embryonic stem (ES) cells and mice, which carry Y5477A/Y5523A/Y5563A mutations in the enzymatic SET domain of the MLL4 protein...
December 21, 2016: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28003272/cancer-specific-changes-in-dna-methylation-reveal-aberrant-silencing-and-activation-of-enhancers-in-leukemia
#9
Ying Qu, Lee Siggens, Lina Cordeddu, Verena I Gaidzik, Kasper Karlsson, Lars Bullinger, Konstanze Döhner, Karl Ekwall, Sören Lehmann, Andreas Lennartsson
Acute myeloid leukemia (AML) is characterized by an impaired differentiation process leading to an accumulation of immature blasts in the blood. One feature of cytogenetically normal AML is alterations to the DNA methylome. Here we have analyzed 57 AML patients with normal karyotype using Illuminas 450 k array and show that aberrant DNA methylation is significantly altered at enhancer regions and that the methylation levels at specific enhancers predict overall survival of AML patients. The majority of sites that become differentially methylated in AML occur in regulatory elements of the human genome...
December 21, 2016: Blood
https://www.readbyqxmd.com/read/28002799/induction-of-specific-t-helper-9-cells-to-inhibit-glioma-cell-growth
#10
Haiyan Zheng, Baohua Yang, Dedong Xu, Wenbo Wang, Jie Tan, Liyuan Sun, Qinghua Li, Li Sun, Xuewei Xia
The effects of Staphylococcal enterotoxin B (SEB) on regulation of immune response have been recognized; whether SEB can enhance the effects of immunotherapy on glioma remains to be investigated. This study tests a hypothesis that administration with SEB enhances the effects of specific immunotherapy on glioma growth in mice. In this study, a glioma-bearing mouse model was developed by adoptive transfer with GL261 cells (a mouse glioma cell line). The mice were treated with the GL261 cell extracts (used as an Ag) with or without administration of SEB...
December 16, 2016: Oncotarget
https://www.readbyqxmd.com/read/27974677/histone-demethylase-lysine-demethylase-5b-in-development-and-cancer
#11
REVIEW
Mengjiao Han, Wenxia Xu, Pu Cheng, Hongchuan Jin, Xian Wang
Histone methylation is one of the most important chromatin posttranslational modifications. It has a range of influences on nuclear functions including epigenetic inheritance, transcriptional regulation and the maintenance of genome integrity. Changes in histone methylation status take part in various physiological and pathological processes. KDM5B (lysine demethylase 5B, also called JARID1B or PLU-1) encodes the histone H3 lysine4 (H3K4) demethylase and exhibits a strong transcriptional repression activity...
December 10, 2016: Oncotarget
https://www.readbyqxmd.com/read/27926873/foxa1-directs-h3k4-monomethylation-at-enhancers-via-recruitment-of-the-methyltransferase-mll3
#12
Kamila M Jozwik, Igor Chernukhin, Aurelien A Serandour, Sankari Nagarajan, Jason S Carroll
FOXA1 is a pioneer factor that binds to enhancer regions that are enriched in H3K4 mono- and dimethylation (H3K4me1 and H3K4me2). We performed a FOXA1 rapid immunoprecipitation mass spectrometry of endogenous proteins (RIME) screen in ERα-positive MCF-7 breast cancer cells and found histone-lysine N-methyltransferase (MLL3) as the top FOXA1-interacting protein. MLL3 is typically thought to induce H3K4me3 at promoter regions, but recent findings suggest it may contribute to H3K4me1 deposition. We performed MLL3 chromatin immunoprecipitation sequencing (ChIP-seq) in breast cancer cells, and MLL3 was shown to occupy regions marked by FOXA1 occupancy and H3K4me1 and H3K4me2...
December 6, 2016: Cell Reports
https://www.readbyqxmd.com/read/27924221/targeting-mll1-h3k4-methyltransferase-activity-to-guide-cardiac-lineage-specific-reprogramming-of-fibroblasts
#13
Liu Liu, Ienglam Lei, Hacer Karatas, Yangbing Li, Li Wang, Leonid Gnatovskiy, Yali Dou, Shaomeng Wang, Li Qian, Zhong Wang
Generation of induced cardiomyocytes (iCMs) directly from fibroblasts offers a great opportunity for cardiac disease modeling and cardiac regeneration. A major challenge of iCM generation is the low conversion rate. To address this issue, we attempted to identify small molecules that could potentiate the reprogramming ability towards cardiac fate by removing inhibitory roadblocks. Using mouse embryonic fibroblasts as the starting cell source, we first screened 47 cardiac development related epigenetic and transcription factors, and identified an unexpected role of H3K4 methyltransferase Mll1 and related factor Men1 in inhibiting iCM reprogramming...
2016: Cell Discovery
https://www.readbyqxmd.com/read/27911222/the-histone-methyltransferases-set5-and-set1-have-overlapping-functions-in-gene-silencing-and-telomere-maintenance
#14
Meagan Jezek, Alison Gast, Grace Choi, Rushmie Kulkarni, Jeremiah Quijote, Andrew Graham-Yooll, DoHwan Park, Erin M Green
Genes adjacent to telomeres are subject to transcriptional repression mediated by an integrated set of chromatin modifying and remodeling factors. The telomeres of Saccharomyces cerevisiae have served as a model for dissecting the function of diverse chromatin proteins in gene silencing, and their study has revealed overlapping roles for many chromatin proteins in either promoting or antagonizing gene repression. The H3K4 methyltransferase Set1, which is commonly linked to transcriptional activation, has been implicated in telomere silencing...
December 2, 2016: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/27899593/the-kdm5-family-is-required-for-activation-of-pro-proliferative-cell-cycle-genes-during-adipocyte-differentiation
#15
Ann-Sofie B Brier, Anne Loft, Jesper G S Madsen, Thomas Rosengren, Ronni Nielsen, Søren F Schmidt, Zongzhi Liu, Qin Yan, Hinrich Gronemeyer, Susanne Mandrup
The KDM5 family of histone demethylases removes the H3K4 tri-methylation (H3K4me3) mark frequently found at promoter regions of actively transcribed genes and is therefore generally considered to contribute to corepression. In this study, we show that knockdown (KD) of all expressed members of the KDM5 family in white and brown preadipocytes leads to deregulated gene expression and blocks differentiation to mature adipocytes. KDM5 KD leads to a considerable increase in H3K4me3 at promoter regions; however, these changes in H3K4me3 have a limited effect on gene expression per se...
November 29, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27895715/protein-kinase-msk1-physically-and-functionally-interacts-with-the-kmt2a-mll1-methyltransferase-complex-and-contributes-to-the-regulation-of-multiple-target-genes
#16
Maaike Wiersma, Marianne Bussiere, John A Halsall, Nil Turan, Robert Slany, Bryan M Turner, Karl P Nightingale
BACKGROUND: The KMT2A/MLL1 lysine methyltransferase complex is an epigenetic regulator of selected developmental genes, in part through the SET domain-catalysed methylation of H3K4. It is essential for normal embryonic development and haematopoiesis and frequently mutated in cancer. The catalytic properties and targeting of KMT2A/MLL1 depend on the proteins with which it complexes and the post-translational protein modifications which some of these proteins put in place, though detailed mechanisms remain unclear...
2016: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/27894088/lsd1-binds-to-hpv16-e7-and-promotes-the-epithelial-mesenchymal-transition-in-cervical-cancer-by-demethylating-histones-at-the-vimentin-promoter
#17
Yuan Liu, Yanan Wang, Chunqin Chen, Jiawen Zhang, Wenyan Qian, Yu Dong, Zhiqiang Liu, Xi Zhang, Xiaoyun Wang, Zhenbo Zhang, Xiaobing Shi, Sufang Wu
Lysine-specific demethylase 1 (LSD1), which specifically demethylates histone H3 lysine 4 (H3K4) and lysine 9 (H3K9), is dysregulated in several cancers. We found that ectopic expression of LSD1 in cervical cancer cells promoted invasion and metastasis in vitro and in vivo, reduced the expression of the epithelial marker E-cadherin, and induced the expression of the mesenchymal marker, Vimentin. By contrast, LSD1 knockdown had the opposite effect and attenuated the HPV16 E7-induced epithelial-mesenchymal transition (EMT)...
November 23, 2016: Oncotarget
https://www.readbyqxmd.com/read/27879032/altered-expression-of-brg1-and-histone-demethylases-and-aberrant-h3k4-methylation-in-less-developmentally-competent-embryos-at-the-time-of-embryonic-genome-activation
#18
Werner G Glanzner, Audrey Wachter, Ana Rita S Coutinho, Marcelo S Albornoz, Raj Duggavathi, Paulo B D GonÇAlves, Vilceu Bordignon
Epigenetics is a fundamental regulator underlying many biological functions, such as development and cell differentiation. Epigenetic modifications affect key chromatin regulation, including transcription and DNA repair, which are critical for normal embryo development. In this study, we profiled the expression of epigenetic modifiers and patterns of epigenetic changes in porcine embryos around the period of embryonic genome activation (EGA). We observed that Brahma-related gene 1 (BRG1) and Lysine demethylase 1A (KDM1A), which can alter the methylation status of lysine 4 in histone 3 (H3K4), localize to the nucleus at Day 3-4 of development...
November 23, 2016: Molecular Reproduction and Development
https://www.readbyqxmd.com/read/27855638/alteration-of-histone-h3k4-methylation-in-glomerular-podocytes-associated-with-proteinuria-in-patients-with-membranous-nephropathy
#19
Takayuki Fujino, Naoyuki Hasebe
BACKGROUND: Histone H3K4 trimethylation (H3K4 me3) is found in active euchromatic regions and plays an important role in podocyte function in which actin filaments are abundant in the foot processes. The pathogenesis of membranous nephropathy (MN), the most prevalent cause of primary nephrotic syndrome in the middle-aged and elderly, is podocyte dysfunction. METHODS: We investigated the role of H3K4 me3 in podocyte dysfunction in nephrotic syndrome using cultured podocytes and a mouse proteinuria model induced by LPS...
November 17, 2016: BMC Nephrology
https://www.readbyqxmd.com/read/27855486/yin-yang-actions-of-histone-methylation-regulatory-complexes-in-the-brain
#20
Patricia Marie Garay, Margarete Aryanka Wallner, Shigeki Iwase
Dysregulation of histone methylation has emerged as a major driver of neurodevelopmental disorders including intellectual disabilities and autism spectrum disorders. Histone methyl writer and eraser enzymes generally act within multisubunit complexes rather than in isolation. However, it remains largely elusive how such complexes cooperate to achieve the precise spatiotemporal gene expression in the developing brain. Histone H3K4 methylation (H3K4me) is a chromatin signature associated with active gene-regulatory elements...
December 2016: Epigenomics
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