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https://www.readbyqxmd.com/read/28526911/dynamics-of-post-translationally-modified-histones-during-barley-pollen-embryogenesis-in-the-presence-or-absence-of-the-epi-drug-trichostatin-a
#1
Pooja Pandey, Diaa S Daghma, Andreas Houben, Jochen Kumlehn, Michael Melzer, Twan Rutten
Improving pollen embryogenesis. Despite the agro-economic importance of pollen embryogenesis, the mechanisms underlying this process are still poorly understood. We describe the dynamics of chromatin modifications (histones H3K4me2, H3K9ac, H3K9me2, and H3K27me3) and chromatin marks (RNA polymerase II CDC phospho-Ser5, and CENH3) during barley pollen embryogenesis. Immunolabeling results show that, in reaction to stress, immature pollen rapidly starts reorganizing several important chromatin modifications indicative of a change in cell fate...
May 19, 2017: Plant Reproduction
https://www.readbyqxmd.com/read/28522800/single-cell-single-mrna-analysis-of-ccnb1-promoter-regulation
#2
Nidhi Vishnoi, Jie Yao
Promoter activation drives gene transcriptional output. Here we report generating site-specifically integrated single-copy promoter transgenes and measuring their expression to indicate promoter activities at single-mRNA level. mRNA counts, Pol II density and Pol II firing rates of the Ccnb1 promoter transgene resembled those of the native Ccnb1 gene both among asynchronous cells and during the cell cycle. We observed distinct activation states of the Ccnb1 promoter among G1 and G2/M cells, suggesting cell cycle-independent origin of cell-to-cell variation in Ccnb1 promoter activation...
May 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28517045/set-domain-group701-encodes-a-h3k4-methytransferase-and-regulates-multiple-key-processes-of-rice-plant-development
#3
Kunpeng Liu, Yu Yu, Aiwu Dong, Wen-Hui Shen
Chromatin-based epigenetic information plays an important role in developmental gene regulation, in response to environment, and in natural variation of gene expression levels. Histone H3 lysine 4 di/trimethylation (H3K4me2/3) is abundant in euchromatin and is generally associated with transcriptional activation. Strikingly, however, enzymes catalyzing H3K4me2/3 remain poorly characterized in crops so far. Here, we investigated the function of the rice SET DOMAIN GROUP 701 (SDG701) gene by molecular and biochemical characterization of the gene product, and by studying effects of its loss or gain of function on plant growth and development...
May 18, 2017: New Phytologist
https://www.readbyqxmd.com/read/28506463/rna-pol-ii-dynamics-modulate-co-transcriptional-chromatin-modification-ctd-phosphorylation-and-transcriptional-direction
#4
Nova Fong, Tassa Saldi, Ryan M Sheridan, Michael A Cortazar, David L Bentley
Eukaryotic genes are marked by conserved post-translational modifications on the RNA pol II C-terminal domain (CTD) and the chromatin template. How the 5'-3' profiles of these marks are established is poorly understood. Using pol II mutants in human cells, we found that slow transcription repositioned specific co-transcriptionally deposited chromatin modifications; histone H3 lysine 36 trimethyl (H3K36me3) shifted within genes toward 5' ends, and histone H3 lysine 4 dimethyl (H3K4me2) extended farther upstream of start sites...
May 18, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28498828/kdm1a-lsd1-regulates-the-differentiation-and-maintenance-of-spermatogonia-in-mice
#5
Dexter A Myrick, Michael A Christopher, Alyssa M Scott, Ashley K Simon, Paul G Donlin-Asp, William G Kelly, David J Katz
The proper regulation of spermatogenesis is crucial to ensure the continued production of sperm and fertility. Here, we investigated the function of the H3K4me2 demethylase KDM1A/LSD1 during spermatogenesis in developing and adult mice. Conditional deletion of Kdm1a in the testis just prior to birth leads to fewer spermatogonia and germ cell loss before 3 weeks of age. These results demonstrate that KDM1A is required for spermatogonial differentiation, as well as germ cell survival, in the developing testis...
2017: PloS One
https://www.readbyqxmd.com/read/28481366/the-zinc-finger-transcriptional-factor-slug-transcriptionally-downregulates-er%C3%AE-by-recruiting-lysine-specific-demethylase-1-in-human-breast-cancer
#6
J-W Bai, M-N Chen, X-L Wei, Y-Ch Li, H-Y Lin, M Chen, J-W Li, C-W Du, K Man, G-J Zhang
Estrogen receptor α (ERα) is related with epithelial-mesenchymal transition, invasion and metastasis, and serves as an important therapeutic predictor and prognostic factor in breast cancer patients. The triple negative breast cancer (TNBC) is characterized by loss of hormone receptors and human epidermal growth factor receptor 2 (Her2), and lacks effective targeted therapy with poor prognosis. Unfortunately, the molecular mechanisms of ERα deficiency, which becomes hormone independent and results in resistance to endocrine therapy, remain to be elucidated in breast cancer...
May 8, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28476938/chromatin-organization-at-the-nuclear-periphery-as-revealed-by-image-analysis-of-structured-illumination-microscopy-data
#7
Jindřiška Fišerová, Michaela Efenberková, Tomáš Sieger, Miloslava Maninová, Jana Uhlířová, Pavel Hozák
Nuclear periphery (NP) plays substantial role in chromatin organization. Heterochromatin at the NP is intermitted with active chromatin surrounding nuclear pore complexes (NPCs), however, details of the peripheral chromatin organization are missing. To discern the distributions of epigenetic marks at the NP of HeLa nuclei, we used structured illumination microscopy combined with a new MATLAB software tool for an automatic NP and NPC detection, measurements of fluorescent intensity and statistical analysis of measured data...
May 5, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28468635/prc2-represses-transcribed-genes-on-the-imprinted-inactive-x-chromosome-in-mice
#8
Emily Maclary, Michael Hinten, Clair Harris, Shriya Sethuraman, Srimonta Gayen, Sundeep Kalantry
BACKGROUND: Polycomb repressive complex 2 (PRC2) catalyzes histone H3K27me3, which marks many transcriptionally silent genes throughout the mammalian genome. Although H3K27me3 is associated with silenced gene expression broadly, it remains unclear why some but not other PRC2 target genes require PRC2 and H3K27me3 for silencing. RESULTS: Here we define the transcriptional and chromatin features that predict which PRC2 target genes require PRC2/H3K27me3 for silencing by interrogating imprinted mouse X-chromosome inactivation...
May 3, 2017: Genome Biology
https://www.readbyqxmd.com/read/28450734/modulation-of-gene-expression-dynamics-by-co-transcriptional-histone-methylations
#9
REVIEW
Hyeonju Woo, So Dam Ha, Sung Bae Lee, Stephen Buratowski, TaeSoo Kim
Co-transcriptional methylations of histone H3 at lysines 4 and 36, highly conserved methyl marks from yeast to humans, have profound roles in regulation of histone acetylation. These modifications function to recruit and/or activate distinct histone acetyltransferases (HATs) or histone deacetylases (HDACs). Whereas H3K4me3 increases acetylation at promoters via multiple HATs, H3K4me2 targets Set3 HDAC to deacetylate histones in 5' transcribed regions. In 3' regions of genes, H3K36me2/3 facilitates deacetylation by Rpd3S HDAC and slows elongation...
April 28, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28445736/systematic-epigenomic-analysis-reveals-chromatin-states-associated-with-melanoma-progression
#10
Petko Fiziev, Kadir C Akdemir, John P Miller, Emily Z Keung, Neha S Samant, Sneha Sharma, Christopher A Natale, Christopher J Terranova, Mayinuer Maitituoheti, Samirkumar B Amin, Emmanuel Martinez-Ledesma, Mayura Dhamdhere, Jacob B Axelrad, Amiksha Shah, Christine S Cheng, Harshad Mahadeshwar, Sahil Seth, Michelle C Barton, Alexei Protopopov, Kenneth Y Tsai, Michael A Davies, Benjamin A Garcia, Ido Amit, Lynda Chin, Jason Ernst, Kunal Rai
The extent and nature of epigenomic changes associated with melanoma progression is poorly understood. Through systematic epigenomic profiling of 35 epigenetic modifications and transcriptomic analysis, we define chromatin state changes associated with melanomagenesis by using a cell phenotypic model of non-tumorigenic and tumorigenic states. Computation of specific chromatin state transitions showed loss of histone acetylations and H3K4me2/3 on regulatory regions proximal to specific cancer-regulatory genes in important melanoma-driving cell signaling pathways...
April 25, 2017: Cell Reports
https://www.readbyqxmd.com/read/28442058/nuclear-transfer-alters-placental-gene-expression-and-associated-histone-modifications-of-the-placental-specific-imprinted-gene-pleckstrin-homology-like-domain-family-a-member-2-phlda2-in-cattle
#11
Daniel R Arnold, Roberta C Gaspar, Carlos V da Rocha, Juliano R Sangalli, Tiago H C de Bem, Carolina A P Corrêa, João C T Penteado, Flavio V Meirelles, Flavia L Lopes
Abnormal placental development is frequent in nuclear transfer (NT) pregnancies and is likely to be associated with altered epigenetic reprogramming. In the present study, fetal and placental measurements were taken on Day 60 of gestation in cows with pregnancies produced by AI, IVF and NT. Placentas were collected and subjected to histological evaluation, the expression of genes important in trophoblast differentiation and expression of the placental imprinted gene pleckstrin homology-like domain, family A, member 2 (PHLDA2), as well as chromatin immunoprecipitation (ChIP) for histone marks within the promoter of PHLDA2...
March 2017: Reproduction, Fertility, and Development
https://www.readbyqxmd.com/read/28413450/fetal-testis-organ-culture-reproduces-the-dynamics-of-epigenetic-reprogramming-in-rat-gonocytes
#12
Arlette Rwigemera, Fabien Joao, Geraldine Delbes
BACKGROUND: Epigenetic reprogramming is a critical step in male germ cell development that occurs during perinatal life. It is characterized by the remodeling of different epigenetic marks such as DNA methylation (5mC) and methylation of histone H3. It has been suggested that endocrine disruptors can affect the male germline epigenome by altering epigenetic reprogramming, but the mechanisms involved are still unknown. We have previously used an organ culture system that maintains the development of the different fetal testis cell types, to evaluate the effects of various endocrine disruptors on gametogenesis and steroidogenesis in the rat...
2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/28404874/identification-of-jl1037-as-a-novel-specific-reversible-lysine-specific-demethylase-1-inhibitor-that-induce-apoptosis-and-autophagy-of-aml-cells
#13
Shuang Liu, Wenting Lu, Shouyun Li, Saisai Li, Jia Liu, Yuanyuan Xing, Shuzu Zhang, Joe Zhongxiang Zhou, Haiyan Xing, Yingxi Xu, Qing Rao, Chengjun Deng, Min Wang, Jianxiang Wang
Lysine-specific demethylase 1 (LSD1) has been recognized as a potential therapeutic target for acute myeloid leukemia (AML). Herein, we identified a novel LSD1 inhibitor, JL1037, via Computer Aided Drug Design technology. JL1037 is a potent, selective and reversible LSD1 inhibitor with IC50s of 0.1 μM and >1.5 μM for LSD1 and monoamine oxidases A/B (MAO-A/B), respectively. Treatment of THP-1 and Kasumi-1 cell lines with JL1037 resulted in dose dependent accumulation of H3K4me1 and H3K4me2, the major substrates of LSD1, as well as inhibition of cell proliferation, blockade of cell cycle and induction of apoptosis...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28390942/fluorinated-tranylcypromine-analogues-as-inhibitors-of-lysine-specific-demethylase-1-lsd1-kdm1a
#14
Maria Teresa Borrello, Benjamin Schinor, Katharina Bartels, Hanae Benelkebir, Sara Pereira, Wafa T Al-Jamal, Leon Douglas, Patrick J Duriez, Graham Packham, Günter Haufe, A Ganesan
We report a series of tranylcypromine analogues containing a fluorine in the cyclopropyl ring. A number of compounds with additional m- or p-substitution of the aryl ring were micromolar inhibitors of the LSD1 enzyme. In cellular assays, the compounds inhibited the proliferation of acute myeloid leukemia cell lines. Increased levels of the biomarkers H3K4me2 and CD86 were consistent with LSD1 target engagement.
March 29, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28381181/effect-of-histone-modifications-on-hmlh1-alternative-splicing-in-gastric-cancer
#15
Jin-Xuan Zhao, Xiao-Wei Li, Bing-Yu Shi, Fang Wang, Zheng-Rong Xu, Hai-Lan Meng, Yun-Yan Su, Jing-Mei Wang, Nong Xiao, Qiong He, Ya-Ping Wang, Yi-Mei Fan
hMLH1 is one of the mismatch genes closely related to the occurrence of gastric cancer. Epigenetic regulation may play more important roles than gene mutations in DNA damage repair genes to drive carcinogenesis. In this article, we discuss the role of epigenetic changes, especially histone modifications in the regulation of hMLH1 alternative splicing. Our results showed that hMLH1 delEx10, delEx11, delEx10-11, delEx16 and delEx17 transcripts were ubiquitous in sporadic Chinese gastric cancer patients and gastric cancer cell lines...
April 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28360266/gene-bivalency-at-polycomb-domains-regulates-cranial-neural-crest-positional-identity
#16
Maryline Minoux, Sjoerd Holwerda, Antonio Vitobello, Taro Kitazawa, Hubertus Kohler, Michael B Stadler, Filippo M Rijli
The cranial neural crest cells are multipotent cells that provide head skeletogenic mesenchyme and are crucial for craniofacial patterning. We analyzed the chromatin landscapes of mouse cranial neural crest subpopulations in vivo. Early postmigratory subpopulations contributing to distinct mouse craniofacial structures displayed similar chromatin accessibility patterns yet differed transcriptionally. Accessible promoters and enhancers of differentially silenced genes carried H3K27me3/H3K4me2 bivalent chromatin marks embedded in large enhancer of zeste homolog 2-dependent Polycomb domains, indicating transcriptional poising...
March 31, 2017: Science
https://www.readbyqxmd.com/read/28289232/transcriptional-landscape-of-the-human-cell-cycle
#17
Yin Liu, Sujun Chen, Su Wang, Fraser Soares, Martin Fischer, Feilong Meng, Zhou Du, Charles Lin, Clifford Meyer, James A DeCaprio, Myles Brown, X Shirley Liu, Housheng Hansen He
Steady-state gene expression across the cell cycle has been studied extensively. However, transcriptional gene regulation and the dynamics of histone modification at different cell-cycle stages are largely unknown. By applying a combination of global nuclear run-on sequencing (GRO-seq), RNA sequencing (RNA-seq), and histone-modification Chip sequencing (ChIP-seq), we depicted a comprehensive transcriptional landscape at the G0/G1, G1/S, and M phases of breast cancer MCF-7 cells. Importantly, GRO-seq and RNA-seq analysis identified different cell-cycle-regulated genes, suggesting a lag between transcription and steady-state expression during the cell cycle...
March 28, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28284523/demethylase-kdm6a-epigenetically-promotes-il-6-and-ifn-%C3%AE-production-in-macrophages
#18
Xia Li, Qian Zhang, Qingzhu Shi, Yin Liu, Kai Zhao, Qicong Shen, Yang Shi, Xingguang Liu, Chunmei Wang, Nan Li, Yuanfang Ma, Xuetao Cao
Molecular regulation of innate signal-initiated proinflammatory cytokine production has been extensively investigated. However, the roles of epigenetic modifiers and their underlying mechanisms in regulating innate inflammatory response and development of autoimmune diseases need to be further understood. Demethylase Kdm6a promotes gene transcription in cell-lineage specification through demethylating histone H3 lysine di/tri-methylation (H3K27me2/3), and loss of Kdm6a results in developmental defects. However, the function of Kdm6a in innate immunity and inflammation remains largely unknown...
March 8, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28266526/elf-mf-exposure-affects-the-robustness-of-epigenetic-programming-during-granulopoiesis
#19
Melissa Manser, Mohamad R Abdul Sater, Christoph D Schmid, Faiza Noreen, Manuel Murbach, Niels Kuster, David Schuermann, Primo Schär
Extremely-low-frequency magnetic fields (ELF-MF) have been classified as "possibly carcinogenic" to humans on the grounds of an epidemiological association of ELF-MF exposure with an increased risk of childhood leukaemia. Yet, underlying mechanisms have remained obscure. Genome instability seems an unlikely reason as the energy transmitted by ELF-MF is too low to damage DNA and induce cancer-promoting mutations. ELF-MF, however, may perturb the epigenetic code of genomes, which is well-known to be sensitive to environmental conditions and generally deranged in cancers, including leukaemia...
March 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28219005/a-rhodium-iii-based-inhibitor-of-lysine-specific-histone-demethylase-1-as-an-epigenetic-modulator-in-prostate-cancer-cells
#20
Chao Yang, Wanhe Wang, Jia-Xin Liang, Guodong Li, Kasipandi Vellaisamy, Chun-Yuen Wong, Dik-Lung Ma, Chung-Hang Leung
We report herein a novel rhodium(III) complex 1 as a new LSD1 targeting agent and epigenetic modulator. Complex 1 disrupted the interaction of LSD1-H3K4me2 in human prostate carcinoma cells and enhanced the amplification of p21, FOXA2, and BMP2 gene promoters. Complex 1 was selective for LSD1 over other histone demethylases, such as KDM2b, KDM7, and MAO activities, and also showed antiproliferative activity toward human cancer cells. To date, complex 1 is the first metal-based inhibitor of LSD1 activity.
March 1, 2017: Journal of Medicinal Chemistry
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