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chromatin remodeling

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https://www.readbyqxmd.com/read/29160132/active-h3k27me3-demethylation-by-kdm6b-is-required-for-normal-development-of-bovine-preimplantation-embryos
#1
Nhi Chung, Yanina S Bogliotti, Wei Ding, Marcela Vilarino, Kazuki Takahashi, James L Chitwood, Richard M Schultz, Pablo J Ross
The substantial epigenetic remodeling that occurs during early stages of mammalian embryonic development likely contributes to reprogramming the parental genomes from a differentiated to a totipotent state and activation of the embryonic genome. Trimethylation of lysine 27 of histone 3 (H3K27me3) is a repressive mark that undergoes global dynamic changes during preimplantation development of several species. To ascertain the role of H3K27me3 in bovine preimplantation development we perturbed the activity of KDM6B, which demethylates H3K27me3...
November 21, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/29158441/shep-regulates-drosophila-neuronal-remodeling-by-controlling-transcription-of-its-chromatin-targets
#2
Dahong Chen, Ryan K Dale, Elissa P Lei
Neuronal remodeling is critical to form the mature nervous system and can lead to neuropsychiatric diseases when disrupted. Global gene expression changes in neurons during remodeling as well as the factors that regulate these changes remain poorly defined. To elucidate this process, we performed RNA-seq on isolated Drosophila larval and pupal neurons and found up-regulated synaptic signaling and down-regulated gene expression regulators as a result of normal neuronal metamorphosis. We further tested the role of alan shepard (shep), which encodes an evolutionarily conserved RNA-binding protein required for proper neuronal remodeling...
November 20, 2017: Development
https://www.readbyqxmd.com/read/29156698/combined-brd4-and-cdk9-inhibition-as-a-new-therapeutic-approach-in-malignant-rhabdoid-tumors
#3
Natalia Moreno, Till Holsten, Julius Mertins, Annabelle Zhogbi, Pascal Johann, Marcel Kool, Michael Meisterernst, Kornelius Kerl
Rhabdoid tumors are caused by the deletion of SMARCB1, whose protein encodes the SMARCB1 subunit of the chromatin remodeling complex SWI/SNF that is involved in global chromatin organization and gene expression control. Simultaneously inhibiting the main players involved in the deregulated transcription machinery is a promising option for preventing exaggerated tumor cell proliferation and survival as it may bypass compensatory mechanisms. In support of this hypothesis, we report efficient impairment of cellular proliferation and strong induction of cell death elicited by inhibition of bromodomain protein BRD4 and transcription kinase CDK9 using small molecular compounds...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29155983/meox1-accelerates-myocardial-hypertrophic-decompensation-through-gata4
#4
Dan Lu, Jizheng Wang, Jing Li, Feifei Guan, Xu Zhang, Wei Dong, Ning Liu, Shan Gao, Lianfeng Zhang
Aims: Pathological hypertrophy is the result of gene network regulation, which ultimately leads to adverse cardiac remodelling and heart failure (HF), and is accompanied by the reactivation of a 'foetal gene programme'. The Mesenchyme homeobox 1 (Meox1) gene is one of the foetal programme genes. Meox1 may play a role in embryonic development, but its regulation of pathological hypertrophy is not known. Therefore, this study investigated the effect of Meox1 on pathological hypertrophy, including familial and pressure overload-induced hypertrophy, and its potential mechanism of action...
November 16, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/29155171/manganese-chloride-induces-histone-acetylation-changes-in-neuronal-cells-its-role-in-manganese-induced-damage
#5
Zhenkun Guo, Zhipeng Zhang, Qingqing Wang, Jie Zhang, Lijin Wang, Qunwei Zhang, Huangyuan Li, Siying Wu
Manganese neurotoxicity presents with Parkinson-like symptoms, with degeneration of dopaminergic neurons in the basal ganglia as the principal pathological feature. Manganese neurotoxicity studies may contribute to a better understanding of the mechanism of Parkinson's disease. Here, we examined the effects of manganese on histone acetylation, a major epigenetic change in chromatin that can regulate gene expression, chromatin remodelling, cell cycle progression, DNA repair and apoptosis. In this study, we found that manganese chloride (MnCl2) may significantly suppress the acetylation of histone H3 and H4 in PC12 cells and SHSY5Y cells in a time-dependent manner...
November 16, 2017: Neurotoxicology
https://www.readbyqxmd.com/read/29153839/asymmetry-between-activation-and-deactivation-during-a-transcriptional-pulse
#6
Lee S S Dunham, Hiroshi Momiji, Claire V Harper, Polly J Downton, Kirsty Hey, Anne McNamara, Karen Featherstone, David G Spiller, David A Rand, Bärbel Finkenstädt, Michael R H White, Julian R E Davis
Transcription in eukaryotic cells occurs in gene-specific bursts or pulses of activity. Recent studies identified a spectrum of transcriptionally active "on-states," interspersed with periods of inactivity, but these "off-states" and the process of transcriptional deactivation are poorly understood. To examine what occurs during deactivation, we investigate the dynamics of switching between variable rates. We measured live single-cell expression of luciferase reporters from human growth hormone or human prolactin promoters in a pituitary cell line...
November 13, 2017: Cell Systems
https://www.readbyqxmd.com/read/29153328/tdp-43-promotes-neurodegeneration-by-impairing-chromatin-remodeling
#7
Amit Berson, Ashley Sartoris, Raffaella Nativio, Vivianna Van Deerlin, Jon B Toledo, Sílvia Porta, Shichong Liu, Chia-Yu Chung, Benjamin A Garcia, Virginia M-Y Lee, John Q Trojanowski, F Brad Johnson, Shelley L Berger, Nancy M Bonini
Regulation of chromatin structure is critical for brain development and function. However, the involvement of chromatin dynamics in neurodegeneration is less well understood. Here we find, launching from Drosophila models of amyotrophic lateral sclerosis and frontotemporal dementia, that TDP-43 impairs the induction of multiple key stress genes required to protect from disease by reducing the recruitment of the chromatin remodeler Chd1 to chromatin. Chd1 depletion robustly enhances TDP-43-mediated neurodegeneration and promotes the formation of stress granules...
November 9, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/29152582/the-genomic-landscape-of-the-fungus-specific-swi-snf-complex-subunit-snf6-in-candida-albicans
#8
Faiza Tebbji, Yaolin Chen, Adnane Sellam, Malcolm Whiteway
SWI/SNF is an ATP-dependent chromatin-remodeling complex that is required for the regulation of gene expression in eukaryotes. While most of the fungal SWI/SNF components are evolutionarily conserved with those of the metazoan SWI/SNF, subunits such as Snf6 are specific to certain fungi and thus represent potential antifungal targets. We have characterized the role of the Snf6 protein in Candida albicans. Our data showed that although there was low conservation of its protein sequence with other fungal orthologs, Snf6 was copurified with bona fide SWI/SNF complex subunits...
November 2017: MSphere
https://www.readbyqxmd.com/read/29151933/expression-of-arid1b-is-associated-with-poor-outcomes-and-predicts-the-benefit-from-adjuvant-chemotherapy-in-bladder-urothelial-carcinoma
#9
Beihe Wang, Huyang Xie, Chunguang Ma, Guiming Zhang, Hualei Gan, Qifeng Wang, Xiaohang Liu, Yiping Zhu, Yao Zhu, Guohai Shi, Hailiang Zhang, Bo Dai, Yijun Shen, Dingwei Ye
Background ARID1B, which exists as a mutually exclusive isoform with ARID1A in the SWI/SNF chromatin remodeling complex, has been recently identified as a major mutant gene in a wide variety of cancers. The present study aimed to determine the association between ARID1B expression and outcomes, as well as the benefit from adjuvant chemotherapy in patients with bladder cancer. Methods Tissue microarrays of 143 consecutively recruited patients with bladder cancer from our center were created. Immunohistochemistry was performed to assess the expression of ARID1B and its association with outcomes...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/29149408/function-of-translationally-controlled-tumor-protein-in-organ-growth-lessons-from-drosophila-studies
#10
Kwang-Wook Choi, Sung-Tae Hong, Thao Phuong Le
Regulation of cell growth and proliferation is crucial for development and function of organs in all animals. Genetic defects in growth control can lead to developmental disorders and cancers. Translationally controlled tumor protein (TCTP) is a family of evolutionarily conserved proteins implicated in cancer. Recent studies have revealed multiple roles of TCTP in diverse cellular events, but TCTP functions in vivo are poorly understood in vertebrate systems. We have used Drosophila melanogaster, the fruit fly, as a model organism for genetic dissection of Tctp function...
2017: Results and Problems in Cell Differentiation
https://www.readbyqxmd.com/read/29149203/alc1-chd1l-a-chromatin-remodeling-enzyme-is-required-for-efficient-base-excision-repair
#11
Masataka Tsuda, Kosai Cho, Masato Ooka, Naoto Shimizu, Reiko Watanabe, Akira Yasui, Yuka Nakazawa, Tomoo Ogi, Hiroshi Harada, Keli Agama, Jun Nakamura, Ryuta Asada, Haruna Fujiike, Tetsushi Sakuma, Takashi Yamamoto, Junko Murai, Masahiro Hiraoka, Kaoru Koike, Yves Pommier, Shunichi Takeda, Kouji Hirota
ALC1/CHD1L is a member of the SNF2 superfamily of ATPases carrying a macrodomain that binds poly(ADP-ribose). Poly(ADP-ribose) polymerase (PARP) 1 and 2 synthesize poly(ADP-ribose) at DNA-strand cleavage sites, promoting base excision repair (BER). Although depletion of ALC1 causes increased sensitivity to various DNA-damaging agents (H2O2, UV, and phleomycin), the role played by ALC1 in BER has not yet been established. To explore this role, as well as the role of ALC1's ATPase activity in BER, we disrupted the ALC1 gene and inserted the ATPase-dead (E165Q) mutation into the ALC1 gene in chicken DT40 cells, which do not express PARP2...
2017: PloS One
https://www.readbyqxmd.com/read/29148847/emerging-therapeutic-targets-in-myeloproliferative-neoplasms-and-peripheral-t-cell-leukemia-and-lymphomas
#12
Anna Orlova, Bettina Wingelhofer, Heidi A Neubauer, Barbara Maurer, Angelika Berger-Becvar, György Miklós Keserű, Patrick T Gunning, Peter Valent, Richard Moriggl
Hematopoietic neoplasms are often driven by gain-of-function mutations of the JAK-STAT pathway together with mutations of chromatin remodeling and DNA damage control pathways. The interconnection between the JAK-STAT pathway, epigenetic regulation or DNA damage control is still poorly understood in cancer cell biology. Areas covered: Here, we focus on a broader description of mutational insights into myeloproliferative neoplasms and peripheral T-cell leukemia and lymphomas, since sequencing efforts have identified similar combinations of driver mutations in these diseases covering different lineages...
November 17, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/29145630/yaf9-subunit-of-the-nua4-and-swr1-complexes-targets-histone-h3k27ac-through-its-yeats-domain
#13
Brianna J Klein, Salar Ahmad, Kendra R Vann, Forest H Andrews, Zachary A Mayo, Gaelle Bourriquen, Joseph B Bridgers, Jinyong Zhang, Brian D Strahl, Jacques Côté, Tatiana G Kutateladze
Yaf9 is an integral part of the NuA4 acetyltransferase and the SWR1 chromatin remodeling complexes. Here, we show that Yaf9 associates with acetylated histone H3 with high preference for H3K27ac. The crystal structure of the Yaf9 YEATS domain bound to the H3K27ac peptide reveals that the sequence C-terminal to K27ac stabilizes the complex. The side chain of K27ac inserts between two aromatic residues, mutation of which abrogates the interaction in vitro and leads in vivo to phenotypes similar to YAF9 deletion, including loss of SWR1-dependent incorporation of variant histone H2A...
November 14, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29144820/pheochromocytoma-a-genetic-and-diagnostic-update
#14
Leilani B Mercado-Asis, Katherine I Wolf, Ivana Jochmanova, David Taïeb
OBJECTIVE: Pheochromocytomas and paragangliomas (PPGLs) are neuroendocrine tumors derived from adrenal or extra-adrenal locations, respectively. Upon suspicion of PPGL, specific metabolomic, molecular, biochemical, imaging, and histopathological studies are performed to prove, localize, treat, and monitor disease progression. Recently, improved diagnostic tools allow physicians to accurately diagnose PPGL, even in patients presenting with small (less than 1 cm) or biochemically silent tumors, which previously delayed proper detection and treatment...
November 16, 2017: Endocrine Practice
https://www.readbyqxmd.com/read/29142070/gfap-and-osmr-regulation-by-brg1-and-stat3-via-interchromosomal-gene-clustering-in-astrocytes
#15
Kenji Ito, Azumi Noguchi, Yuichi Uosaki, Testuya Taga, Hirokazu Arakawa, Takumi Takizawa
Long-range chromatin interactions between gene loci in the cell nucleus are important for many biological processes including transcriptional regulation. Previously, we demonstrated that several genes specifically cluster with the astrocyte-specific gene glial fibrillary acidic protein (Gfap) during astrocyte differentiation; however, the molecular mechanisms for gene clustering remain largely unknown. Here we show that brahma-related gene 1 (BRG1), an ATP-dependent chromatin remodeling factor, and the transcription factor STAT3 are required for Gfap and Osmr clustering and enhanced expression through recruitment to STAT3 recognition sequences and that gene clustering occurs prior to transcriptional upregulation...
November 15, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29141224/genetic-and-genomic-characterization-of-462-melanoma-patient-derived-xenografts-tumor-biopsies-and-cell-lines
#16
Bradley Garman, Ioannis N Anastopoulos, Clemens Krepler, Patricia Brafford, Katrin Sproesser, Yuchao Jiang, Bradley Wubbenhorst, Ravi Amaravadi, Joseph Bennett, Marilda Beqiri, David Elder, Keith T Flaherty, Dennie T Frederick, Tara C Gangadhar, Michael Guarino, David Hoon, Giorgos Karakousis, Qin Liu, Nandita Mitra, Nicholas J Petrelli, Lynn Schuchter, Batool Shannan, Carol L Shields, Jennifer Wargo, Brandon Wenz, Melissa A Wilson, Min Xiao, Wei Xu, Xaiowei Xu, Xiangfan Yin, Nancy R Zhang, Michael A Davies, Meenhard Herlyn, Katherine L Nathanson
Tumor-sequencing studies have revealed the widespread genetic diversity of melanoma. Sequencing of 108 genes previously implicated in melanomagenesis was performed on 462 patient-derived xenografts (PDXs), cell lines, and tumors to identify mutational and copy number aberrations. Samples came from 371 unique individuals: 263 were naive to treatment, and 108 were previously treated with targeted therapy (34), immunotherapy (54), or both (20). Models of all previously reported major melanoma subtypes (BRAF, NRAS, NF1, KIT, and WT/WT/WT) were identified...
November 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/29138516/the-functions-and-unique-features-of-long-intergenic-non-coding-rna
#17
REVIEW
Julia D Ransohoff, Yuning Wei, Paul A Khavari
Long intergenic non-coding RNA (lincRNA) genes have diverse features that distinguish them from mRNA-encoding genes and exercise functions such as remodelling chromatin and genome architecture, RNA stabilization and transcription regulation, including enhancer-associated activity. Some genes currently annotated as encoding lincRNAs include small open reading frames (smORFs) and encode functional peptides and thus may be more properly classified as coding RNAs. lincRNAs may broadly serve to fine-tune the expression of neighbouring genes with remarkable tissue specificity through a diversity of mechanisms, highlighting our rapidly evolving understanding of the non-coding genome...
November 15, 2017: Nature Reviews. Molecular Cell Biology
https://www.readbyqxmd.com/read/29138493/suppression-of-srcap-chromatin-remodelling-complex-and-restriction-of-lymphoid-lineage-commitment-by-pcid2
#18
Buqing Ye, Benyu Liu, Liuliu Yang, Guanling Huang, Lu Hao, Pengyan Xia, Shuo Wang, Ying Du, Xiwen Qin, Pingping Zhu, Jiayi Wu, Nobuo Sakaguchi, Junyan Zhang, Zusen Fan
Lymphoid lineage commitment is an important process in haematopoiesis, which forms the immune system to protect the host from pathogen invasion. However, how multipotent progenitors (MPP) switch into common lymphoid progenitors (CLP) or common myeloid progenitors (CMP) during this process remains elusive. Here we show that PCI domain-containing protein 2 (Pcid2) is highly expressed in MPPs. Pcid2 deletion in the haematopoietic system causes skewed lymphoid lineage specification. In MPPs, Pcid2 interacts with the Zinc finger HIT-type containing 1 (ZNHIT1) to block Snf2-related CREBBP activator protein (SRCAP) activity and prevents the deposition of histone variant H2A...
November 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/29136504/arid1a-has-context-dependent-oncogenic-and-tumor-suppressor-functions-in-liver-cancer
#19
Xuxu Sun, Sam C Wang, Yonglong Wei, Xin Luo, Yuemeng Jia, Lin Li, Purva Gopal, Min Zhu, Ibrahim Nassour, Jen-Chieh Chuang, Thomas Maples, Cemre Celen, Liem H Nguyen, Linwei Wu, Shunjun Fu, Weiping Li, Lijian Hui, Feng Tian, Yuan Ji, Shuyuan Zhang, Mahsa Sorouri, Tae Hyun Hwang, Lynda Letzig, Laura James, Zixi Wang, Adam C Yopp, Amit G Singal, Hao Zhu
ARID1A, an SWI/SNF chromatin-remodeling gene, is commonly mutated in cancer and hypothesized to be tumor suppressive. In some hepatocellular carcinoma patients, ARID1A was highly expressed in primary tumors but not in metastatic lesions, suggesting that ARID1A can be lost after initiation. Mice with liver-specific homozygous or heterozygous Arid1a loss were resistant to tumor initiation while ARID1A overexpression accelerated initiation. In contrast, homozygous or heterozygous Arid1a loss in established tumors accelerated progression and metastasis...
November 13, 2017: Cancer Cell
https://www.readbyqxmd.com/read/29134420/co-localization-and-interaction-of-pax5-with-iba1-in-brain-of-mice
#20
Shashank Kumar Maurya, Rajnikant Mishra
The Pax5, a B-cell-Specific Activator Protein (BSAP) and redox-sensitive transcription factor, is expressed in the immune-privileged brain, B-lymphocytes, lymph nodes and spleen. PAX5-mediated immune pathway has also been described in the progression of Glioblastoma multiforme. However, the status of Pax5 and its role in brain immunity are not yet elucidated. In silico analysis of Pax5 interacting proteins predicts its interaction with proteins of cell proliferation, differentiation of hematopoietic cells, neurogenesis and several cell signalling pathways...
November 13, 2017: Cellular and Molecular Neurobiology
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