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Histone lysine demethylase inhibition reprograms prostate cancermetabolism and mechanics.
Chianese Ugo and Papulino Chiara and Passaro Eugenia andEvers Tom Mj and Babaei Mehrad and Toraldo Antonella andDe Marchi Tommaso and Niméus Emma and Carafa Vincenzo andNicoletti Maria Maddalena and Del Gaudio Nunzio andIaccarino Nunzia an
OBJECTIVE: Aberrant activity of androgen receptor (AR) is the primary cause underlying development and progression of prostate cancer (PCa) and castration-resistant PCa (CRPC). Androgen signaling regulates gene transcription and lipid metabolism, facilitating tumor growth and therapy resistance in early and advanced... |
Histone H3K36me2 and H3K36me3 form a chromatin platform essentialfor DNMT3A-dependent DNA methylation in mouse oocytes.
Yano Seiichi at al.
Establishment of the DNA methylation landscape of mammalian oocytes, mediated by the DNMT3A-DNMT3L complex, is crucial for reproduction and development. In mouse oocytes, high levels of DNA methylation occur exclusively in the transcriptionally active regions, with moderate to low levels of methylation in other regi... |
HOTAIR interacts with PRC2 complex regulating the regional preadipocytetranscriptome and human fat distribution.
Kuo Feng-Chih et al.
Mechanisms governing regional human adipose tissue (AT) development remain undefined. Here, we show that the long non-coding RNA HOTAIR (HOX transcript antisense RNA) is exclusively expressed in gluteofemoral AT, where it is essential for adipocyte development. We find that HOTAIR interacts with polycomb repressive ... |
Effects of GSK-J4 on JMJD3 Histone Demethylase in Mouse Prostate Cancer Xenografts
Sanchez A. et al.
Background/aim: Histone methylation status is required to control gene expression. H3K27me3 is an epigenetic tri-methylation modification to histone H3 controlled by the demethylase JMJD3. JMJD3 is dysregulated in a wide range of cancers and has been shown to control the expression of a specific growth-modulato... |
Epigenetic Mechanisms Mediating Cell State Transitions in Chondrocytes
Wuelling M. et al.
Epigenetic modifications play critical roles in regulating cell lineage differentiation, but the epigenetic mechanisms guiding specific differentiation steps within a cell lineage have rarely been investigated. To decipher such mechanisms, we used the defined transition from proliferating (PC) into hypertrophic chon... |
Epigenetic integrity of paternal imprints enhances the developmental
potential of androgenetic haploid embryonic stem cells.
Zhang, Hongling and Li, Yuanyuan and Ma, Yongjian and Lai,
Chongping and Yu, Qian and Shi, Guangyong and Li, Jinsong
The use of two inhibitors of Mek1/2 and Gsk3β (2i) promotes the
generation of mouse diploid and haploid embryonic stem cells (ESCs) from
the inner cell mass of biparental and uniparental blastocysts,
respectively. However, a system enabling long-term maintenance of
imprints in ESCs has proven challenging. Here, we r... |
Cell-type specific transcriptional networks in root xylem adjacent celllayers
Asensi Fabado Maria Amparo et al.
Transport of water, ions and signals from roots to leaves via the xylem vessels is essential for plant life and needs to be tightly regulated. The final composition of the transpiration stream before passage into the shoots is controlled by the xylem-adjacent cell layers, namely xylem parenchyma and pericycle, in th... |
Loss of KMT2C reprograms the epigenomic landscape in hPSCsresulting in NODAL overexpression and a failure of hemogenic endotheliumspecification.
Maurya Shailendra et al.
Germline or somatic variation in the family of KMT2 lysine methyltransferases have been associated with a variety of congenital disorders and cancers. Notably, -fusions are prevalent in 70\% of infant leukaemias but fail to phenocopy short latency leukaemogenesis in mammalian models, suggesting additional factors ar... |
Effects of GSK-J4 on JMJD3 Histone Demethylase in MouseProstate Cancer Xenografts.
Sanchez A. et al.
BACKGROUND/AIM: Histone methylation status is required to control gene expression. H3K27me3 is an epigenetic tri-methylation modification to histone H3 controlled by the demethylase JMJD3. JMJD3 is dysregulated in a wide range of cancers and has been shown to control the expression of a specific growth-modulatory ge... |
Chemokine switch regulated by TGF-β1 in cancer-associated fibroblastsubsets determines the efficacy of chemo-immunotherapy.
Vienot A. et al.
Combining immunogenic cell death-inducing chemotherapies and PD-1 blockade can generate remarkable tumor responses. It is now well established that TGF-β1 signaling is a major component of treatment resistance and contributes to the cancer-related immunosuppressive microenvironment. However, whether TGF-β1... |
Coordination of EZH2 and SOX2 specifies human neural fate decision.
Zhao Yuan et al.
Polycomb repressive complexes (PRCs) are essential in mouse gastrulation and specify neural ectoderm in human embryonic stem cells (hESCs), but the underlying molecular basis remains unclear. Here in this study, by employing an array of different approaches, such as gene knock-out, RNA-seq, ChIP-seq, et al., we unco... |
A regulatory variant at 3q21.1 confers an increased pleiotropic risk forhyperglycemia and altered bone mineral density.
Sinnott-Armstrong, Nasa et al.
Skeletal and glycemic traits have shared etiology, but the underlying genetic factors remain largely unknown. To identify genetic loci that may have pleiotropic effects, we studied Genome-wide association studies (GWASs) for bone mineral density and glycemic traits and identified a bivariate risk locus at 3q21. Usin... |
Functional annotations of three domestic animal genomes provide vitalresources for comparative and agricultural research.
Kern C. et al.
Gene regulatory elements are central drivers of phenotypic variation and thus of critical importance towards understanding the genetics of complex traits. The Functional Annotation of Animal Genomes consortium was formed to collaboratively annotate the functional elements in animal genomes, starting with domesticate... |
The histone modification H3K4me3 is altered at the locus in Alzheimer'sdisease brain.
Smith, Adam et al.
Several epigenome-wide association studies of DNA methylation have highlighted altered DNA methylation in the gene in Alzheimer's disease (AD) brain samples. However, no study has specifically examined histone modifications in the disease. We use chromatin immunoprecipitation-qPCR to quantify tri-methylation at hist... |
The Essential Function of SETDB1 in Homologous Chromosome Pairing andSynapsis during Meiosis.
Cheng, Ee-Chun et al.
SETDB1 is a histone-lysine N-methyltransferase critical for germline development. However, its function in early meiotic prophase I remains unknown. Here, we report that Setdb1 null spermatocytes display aberrant centromere clustering during leptotene, bouquet formation during zygotene, and subsequent failure in pai... |
The tropical coral displays an unusual chromatin structure and showshistone H3 clipping plasticity upon bleaching.
Roquis D. et al.
is a hermatypic coral with strong ecological importance. Anthropogenic disturbances and global warming are major threats that can induce coral bleaching, the disruption of the mutualistic symbiosis between the coral host and its endosymbiotic algae. Previous works have shown that somaclonal colonies display differen... |
EZH2 and KDM6B Expressions Are Associated with Specific EpigeneticSignatures during EMT in Non Small Cell Lung Carcinomas.
Lachat C. et al.
The role of Epigenetics in Epithelial Mesenchymal Transition (EMT) has recently emerged. Two epigenetic enzymes with paradoxical roles have previously been associated to EMT, EZH2 (Enhancer of Zeste 2 Polycomb Repressive Complex 2 (PRC2) Subunit), a lysine methyltranserase able to add the H3K27me3 mark, and the hist... |
A histone H3.3K36M mutation in mice causes an imbalance of histonemodifications and defects in chondrocyte differentiation.
Abe, Shusaku and Nagatomo, Hiroaki and Sasaki, Hiroyuki and Ishiuchi,Takashi
Histone lysine-to-methionine (K-to-M) mutations have been identified as driver mutations in human cancers. Interestingly, these 'oncohistone' mutations inhibit the activity of histone methyltransferases. Therefore, they can potentially be used as versatile tools to investigate the roles of histone modifications. In ... |
Trans- and cis-acting effects of Firre on epigenetic features of theinactive X chromosome.
Fang, He and Bonora, Giancarlo and Lewandowski, Jordan P and Thakur,Jitendra and Filippova, Galina N and Henikoff, Steven and Shendure, Jay andDuan, Zhijun and Rinn, John L and Deng, Xinxian and Noble, William S andDisteche, Christine M
Firre encodes a lncRNA involved in nuclear organization. Here, we show that Firre RNA expressed from the active X chromosome maintains histone H3K27me3 enrichment on the inactive X chromosome (Xi) in somatic cells. This trans-acting effect involves SUZ12, reflecting interactions between Firre RNA and components of t... |
NSD1-deposited H3K36me2 directs de novo methylation in the mouse malegermline and counteracts Polycomb-associated silencing.
Shirane, Kenjiro and Miura, Fumihito and Ito, Takashi and Lorincz, MatthewC
De novo DNA methylation (DNAme) in mammalian germ cells is dependent on DNMT3A and DNMT3L. However, oocytes and spermatozoa show distinct patterns of DNAme. In mouse oocytes, de novo DNAme requires the lysine methyltransferase (KMTase) SETD2, which deposits H3K36me3. We show here that SETD2 is dispensable for de nov... |
Distinct and temporary-restricted epigenetic mechanisms regulate human αβ and γδ T cell development
Roels J, Kuchmiy A, De Decker M, et al.
The development of TCRαβ and TCRγδ T cells comprises a step-wise process in which regulatory events control differentiation and lineage outcome. To clarify these mechanisms, we employed RNA-sequencing, ATAC-sequencing and ChIPmentation on well-defined thymocyte subsets that represent the conti... |
MeCP2 regulates gene expression through recognition of H3K27me3.
Lee, W and Kim, J and Yun, JM and Ohn, T and Gong, Q
MeCP2 plays a multifaceted role in gene expression regulation and chromatin organization. Interaction between MeCP2 and methylated DNA in the regulation of gene expression is well established. However, the widespread distribution of MeCP2 suggests it has additional interactions with chromatin. Here we demonstra... |
TET-Mediated Hypermethylation Primes SDH-Deficient Cells for HIF2α-Driven Mesenchymal Transition.
Morin A, Goncalves J, Moog S, Castro-Vega LJ, Job S, Buffet A, Fontenille MJ, Woszczyk J, Gimenez-Roqueplo AP, Letouzé E, Favier J
Loss-of-function mutations in the SDHB subunit of succinate dehydrogenase predispose patients to aggressive tumors characterized by pseudohypoxic and hypermethylator phenotypes. The mechanisms leading to DNA hypermethylation and its contribution to SDH-deficient cancers remain undemonstrated. We examine th... |
Alu retrotransposons modulate Nanog expression through dynamic changes in regional chromatin conformation via aryl hydrocarbon receptor.
González-Rico FJ, Vicente-García C, Fernández A, Muñoz-Santos D, Montoliu L, Morales-Hernández A, Merino JM, Román AC, Fernández-Salguero PM
Transcriptional repression of Nanog is an important hallmark of stem cell differentiation. Chromatin modifications have been linked to the epigenetic profile of the Nanog gene, but whether chromatin organization actually plays a causal role in Nanog regulation is still unclear. Here, we report that the formation of ... |
Inhibition of methyltransferase activity of enhancer of zeste 2 leads to enhanced lipid accumulation and altered chromatin status in zebrafish.
den Broeder MJ, Ballangby J, Kamminga LM, Aleström P, Legler J, Lindeman LC, Kamstra JH
BACKGROUND: Recent studies indicate that exposure to environmental chemicals may increase susceptibility to developing metabolic diseases. This susceptibility may in part be caused by changes to the epigenetic landscape which consequently affect gene expression and lead to changes in lipid metabolism. The epigenetic... |
Polycomb Group Proteins Regulate Chromatin Architecture in Mouse Oocytes and Early Embryos.
Du Z, Zheng H, Kawamura YK, Zhang K, Gassler J, Powell S, Xu Q, Lin Z, Xu K, Zhou Q, Ozonov EA, Véron N, Huang B, Li L, Yu G, Liu L, Au Yeung WK, Wang P, Chang L, Wang Q, He A, Sun Y, Na J, Sun Q, Sasaki H, Tachibana K, Peters AHFM, Xie W
In mammals, chromatin organization undergoes drastic reorganization during oocyte development. However, the dynamics of three-dimensional chromatin structure in this process is poorly characterized. Using low-input Hi-C (genome-wide chromatin conformation capture), we found that a unique chromatin organization gradu... |
Allelic H3K27me3 to allelic DNA methylation switch maintains noncanonical imprinting in extraembryonic cells
Chen Zhiyuan, Yin Qiangzong, Inoue Azusa, Zhang Chunxia, Zhang Yi
Faithful maintenance of genomic imprinting is essential for mammalian development. While germline DNA methylation–dependent (canonical) imprinting is relatively stable during development, the recently found oocyte-derived H3K27me3-mediated noncanonical imprinting is mostly transient in early embryos, with some... |
Inhibition of Histone Demethylases LSD1 and UTX Regulates ERα Signaling in Breast Cancer.
Benedetti R, Dell'Aversana C, De Marchi T, Rotili D, Liu NQ, Novakovic B, Boccella S, Di Maro S, Cosconati S, Baldi A, Niméus E, Schultz J, Höglund U, Maione S, Papulino C, Chianese U, Iovino F, Federico A, Mai A, Stunnenberg HG, Nebbioso A, Altucci L
In breast cancer, Lysine-specific demethylase-1 (LSD1) and other lysine demethylases (KDMs), such as Lysine-specific demethylase 6A also known as Ubiquitously transcribed tetratricopeptide repeat, X chromosome (UTX), are co-expressed and co-localize with estrogen receptors (ERs), suggesting the potential use of hybr... |
Transit amplifying cells coordinate mouse incisor mesenchymal stem cell activation.
Walker JV, Zhuang H, Singer D, Illsley CS, Kok WL, Sivaraj KK, Gao Y, Bolton C, Liu Y, Zhao M, Grayson PRC, Wang S, Karbanová J, Lee T, Ardu S, Lai Q, Liu J, Kassem M, Chen S, Yang K, Bai Y, Tredwin C, Zambon AC, Corbeil D, Adams R, Abdallah BM, Hu B
Stem cells (SCs) receive inductive cues from the surrounding microenvironment and cells. Limited molecular evidence has connected tissue-specific mesenchymal stem cells (MSCs) with mesenchymal transit amplifying cells (MTACs). Using mouse incisor as the model, we discover a population of MSCs neibouring to the MTACs... |
The Toxoplasma effector TEEGR promotes parasite persistence by modulating NF-κB signalling via EZH2.
Braun L, Brenier-Pinchart MP, Hammoudi PM, Cannella D, Kieffer-Jaquinod S, Vollaire J, Josserand V, Touquet B, Couté Y, Tardieux I, Bougdour A, Hakimi MA
The protozoan parasite Toxoplasma gondii has co-evolved with its homeothermic hosts (humans included) strategies that drive its quasi-asymptomatic persistence in hosts, hence optimizing the chance of transmission to new hosts. Persistence, which starts with a small subset of parasites that escape host immune killing... |
Kdm6b regulates context-dependent hematopoietic stem cell self-renewal and leukemogenesis.
Mallaney C, Ostrander EL, Celik H, Kramer AC, Martens A, Kothari A, Koh WK, Haussler E, Iwamori N, Gontarz P, Zhang B, Challen GA
The histone demethylase KDM6B (JMJD3) is upregulated in blood disorders, suggesting that it may have important pathogenic functions. Here we examined the function of Kdm6b in hematopoietic stem cells (HSC) to evaluate its potential as a therapeutic target. Loss of Kdm6b lead to depletion of phenotypic and functional... |
H3K27me3 is an epigenetic barrier while KDM6A overexpression improves nuclear reprogramming efficiency.
Zhou C, Wang Y, Zhang J, Su J, An Q, Liu X, Zhang M, Wang Y, Liu J, Zhang Y
Aberrant epigenetic reprogramming is a major factor of developmental failure of cloned embryos. Histone H3 lysine 27 trimethylation (H3K27me3), a histone mark for transcriptional repression, plays important roles in mammalian embryonic development and induced pluripotent stem cell (iPSC) generation. The global loss ... |
Comprehensive Analysis of Chromatin States in Atypical Teratoid/Rhabdoid Tumor Identifies Diverging Roles for SWI/SNF and Polycomb in Gene Regulation.
Erkek S, Johann PD, Finetti MA, Drosos Y, Chou HC, Zapatka M, Sturm D, Jones DTW, Korshunov A, Rhyzova M, Wolf S, Mallm JP, Beck K, Witt O, Kulozik AE, F |
