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https://www.readbyqxmd.com/read/29786770/the-extract-of-leonurus-sibiricus-transgenic-roots-with-atpap1-transcriptional-factor-induces-apoptosis-via-dna-damage-and-down-regulation-of-selected-epigenetic-factors-in-human-cancer-cells
#1
Przemysław Sitarek, Tomasz Kowalczyk, Simona Santangelo, Adam J Białas, Monika Toma, Joanna Wieczfinska, Tomasz Śliwiński, Ewa Skała
The aim of this study was to determine the anticancer potential of Leonurus sibiricus extract derived from in vitro transgenic roots transformed by Agrobacetrium rhizogenes with AtPAP1 transcriptional factor, and that of transformed roots without construct, on grade IV human glioma cells and the U87MG cell line, and attempt to characterize the mechanism involved in this process. The anticancer effect induced by the tested extracts was associated with DNA damage, PARP cleavage/increased H2A.X histone levels and UHRF-1/DNMT1 down-regulation of mRNA levels...
May 21, 2018: Neurochemical Research
https://www.readbyqxmd.com/read/29785026/resetting-the-epigenetic-balance-of-polycomb-and-compass-function-at-enhancers-for-cancer-therapy
#2
Lu Wang, Zibo Zhao, Patrick A Ozark, Damiano Fantini, Stacy A Marshall, Emily J Rendleman, Kira A Cozzolino, Nundia Louis, Xingyao He, Marc A Morgan, Yoh-Hei Takahashi, Clayton K Collings, Edwin R Smith, Panagiotis Ntziachristos, Jeffrey N Savas, Lihua Zou, Rintaro Hashizume, Joshua J Meeks, Ali Shilatifard
The lysine methyltransferase KMT2C (also known as MLL3), a subunit of the COMPASS complex, implements monomethylation of Lys4 on histone H3 (H3K4) at gene enhancers. KMT2C (hereafter referred to as MLL3) frequently incurs point mutations across a range of human tumor types, but precisely how these lesions alter MLL3 function and contribute to oncogenesis is unclear. Here we report a cancer mutational hotspot in MLL3 within the region encoding its plant homeodomain (PHD) repeats and demonstrate that this domain mediates association of MLL3 with the histone H2A deubiquitinase and tumor suppressor BAP1...
May 21, 2018: Nature Medicine
https://www.readbyqxmd.com/read/29780501/a-bi-terminal-protein-ligation-strategy-to-probe-chromatin-structure-during-dna-damage
#3
Sinan Kilic, Iuliia Boichenko, Carolin C Lechner, Beat Fierz
The cellular response to DNA damage results in a signaling cascade that primes chromatin for repair. Combinatorial post-translational modifications (PTMs) play an important role in this process by altering the physical properties of chromatin and recruiting downstream factors. One key signal integrator is the histone variant H2A.X, which is phosphorylated at a C-terminal serine (S139ph), and ubiquitylated within its N-terminal tail at lysines 13 and 15 (K13/15ub). How these PTMs directly impact chromatin structure and thereby facilitate DNA repair is not well understood...
April 21, 2018: Chemical Science
https://www.readbyqxmd.com/read/29771500/rational-design-of-cancer-targeted-selenadiazole-derivative-as-efficient-radiosensitizer-for-precise-cancer-therapy
#4
Delong Zeng, Shulin Deng, Chengcheng Sang, Jianfu Zhao Zhao, Tianfeng Chen
Chemical drug design based on the biochemical characteristics of cancer cells has become an important strategy for discovery of targeted therapies for personalized cancer medicine. Herein, cancer targeting RGD peptide has been covalently conjugated to selenadiazole derivative (RGD-SeD) to improve its cancer selectivity. The RGD decoration significantly enhances the anticancer efficacy of RGD-SeD in αVβ3 integrin-overexpressing HepG2 liver cancer cells, but not in normal liver cells. Cellular uptake assay and fluorescent imaging confirmed the selectivity of RGD-SeD to integrin overexpressing cancer cells...
May 17, 2018: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29770473/icotinib-enhances-lung-cancer-cell-radiosensitivity-in-vitro-and-in-vivo-by-inhibiting-mapk-erk-and-akt-activation
#5
Yonghong Fu, Sen Zhang, Dongjie Wang, Jing Wang
Icotinib hydrochloride is a small epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) that was developed by Chinese scientists. While clinical trials have revealed its efficacy in the treatment of lung cancer, very little is known about its role in enhancing radiosensitivity. In this study, we investigated the effectiveness of Icotinib in enhancing lung cancer cell radiosensitivity and have detailed its underlying molecular mechanism. The lung cancer cell line H1650 was pretreated with or without Icotinib for 24 hours before radiation, and clonogenic survival assay was performed...
May 16, 2018: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/29769606/malonylation-of-histone-h2a-at-lysine-119-inhibits-bub1-dependent-h2a-phosphorylation-and-chromosomal-localization-of-shugoshin-proteins
#6
Tadashi Ishiguro, Kana Tanabe, Yuki Kobayashi, Shinsuke Mizumoto, Motomu Kanai, Shigehiro A Kawashima
Post-translational modifications of histones, such as acetylation and phosphorylation, are highly conserved in eukaryotes and their combination enables precise regulation of many cellular functions. Recent studies using mass spectrometry have revealed various non-acetyl acylations in histones, including malonylation and succinylation, which change the positive charge of lysine into a negative one. However, the molecular function of histone malonylation or succinylation is poorly understood. Here, we discovered the functions of malonylation in histone H2A at lysine 119 (H2A-K119) in chromosome segregation during mitosis and meiosis...
May 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29765032/pcgf5-is-required-for-neural-differentiation-of-embryonic-stem-cells
#7
Mingze Yao, Xueke Zhou, Jiajian Zhou, Shixin Gong, Gongcheng Hu, Jiao Li, Kaimeng Huang, Ping Lai, Guang Shi, Andrew P Hutchins, Hao Sun, Huating Wang, Hongjie Yao
Polycomb repressive complex 1 (PRC1) is an important regulator of gene expression and development. PRC1 contains the E3 ligases RING1A/B, which monoubiquitinate lysine 119 at histone H2A (H2AK119ub1), and has been sub-classified into six major complexes based on the presence of a PCGF subunit. Here, we report that PCGF5, one of six PCGF paralogs, is an important requirement in the differentiation of mouse embryonic stem cells (mESCs) towards a neural cell fate. Although PCGF5 is not required for mESC self-renewal, its loss blocks mESC neural differentiation by activating the SMAD2/TGF-β signaling pathway...
May 15, 2018: Nature Communications
https://www.readbyqxmd.com/read/29764934/structure-specific-recognition-protein-1-ssrp1-is-an-elongated-homodimer-that-binds-histones
#8
Gabriele Marcianò, Stefano Da Vela, Giancarlo Tria, Dmitri I Svergun, Olwyn Byron, Danny T Huang
The histone chaperone complex facilitates chromatin transcription (FACT) plays important roles in DNA repair, replication, and transcription. In the formation of this complex, structure-specific recognition protein-1 (SSRP1) heterodimerizes with suppressor of Ty 16 (SPT16). SSRP1 also has SPT16-independent functions, but how SSRP1 functions alone remains elusive. Here, using analytical ultracentrifugation (AUC) and small-angle X-ray scattering (SAXS) techniques, we characterized human SSRP1 and that from the amoeba Dictyostelium discoideum and show that both orthologs form an elongated homodimer in solution...
May 15, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29759373/random-motion-of-chromatin-is-influenced-by-lamin-a-interconnections
#9
Fereydoon Taheri, Buse Isbilir, Gabriele Müller, Jan W Krieger, Giuseppe Chirico, Jörg Langowski, Katalin Tóth
Using fluorescence correlation spectroscopy in single-plane illumination microscopy, we investigated the dynamics of chromatin in interphase mouse adult fibroblast cell nuclei under the influence of the intermediate filament protein lamin A. We find that 1) lamin A-eGFP and histone H2A-mRFP show significant comobility, indicating that their motions are clearly interconnected in the nucleus, and 2) that the random motion of histones H2A within the chromatin network is subdiffusive, i.e., the effective diffusion coefficient decreases for slow timescales...
May 11, 2018: Biophysical Journal
https://www.readbyqxmd.com/read/29742439/norc-recruitment-by-h2a-x-deposition-at-rrna-gene-promoter-limits-embryonic-stem-cell-proliferation
#10
Boris Eleuteri, Sergi Aranda, Patrik Ernfors
Embryonic stem cells (ESCs) display an abbreviated cell cycle, resulting in a short doubling time and rapid proliferation. The histone variant H2A.X is critical for proliferation of stem cells, although mechanistic insights have remained obscure. Here, we show that H2A.X defines the rate of mouse ESC proliferation independently of the DNA damage response pathway, and it associates with three major chromatin-modifying complexes. Our functional and biochemical analyses demonstrate that H2A.X-associated factors mediate the H2A...
May 8, 2018: Cell Reports
https://www.readbyqxmd.com/read/29741650/flap-endonuclease-overexpression-drives-genome-instability-and-dna-damage-hypersensitivity-in-a-pcna-dependent-manner
#11
Jordan R Becker, David Gallo, Wendy Leung, Taylor Croissant, Yee Mon Thu, Hai Dang Nguyen, Timothy K Starr, Grant W Brown, Anja-Katrin Bielinsky
Overexpression of the flap endonuclease FEN1 has been observed in a variety of cancer types and is a marker for poor prognosis. To better understand the cellular consequences of FEN1 overexpression we utilized a model of its Saccharomyces cerevisiae homolog, RAD27. In this system, we discovered that flap endonuclease overexpression impedes replication fork progression and leads to an accumulation of cells in mid-S phase. This was accompanied by increased phosphorylation of the checkpoint kinase Rad53 and histone H2A-S129...
May 7, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29738831/histone-variant-h2a-z-antagonizes-the-positive-effect-of-the-transcriptional-activator-cpc1-to-regulate-catalase-3-expression-under-normal-and-oxidative-stress-conditions
#12
Qing Dong, Yajun Wang, Shaohua Qi, Kexin Gai, Qun He, Ying Wang
In eukaryotes, deposition of the histone variant H2A.Z into nucleosomes through the chromatin remodeling complex, SWR1, is a crucial step in modulating gene transcription. Recently, H2A.Z has been shown to control the expression of responsive genes, but the underlying mechanism of how H2A.Z responds to physiological stimuli is not well understood. Here, we reveal that, in Neurospora crassa, H2A.Z is a negative regulator of catalase-3 gene, which is responsible for resistance to oxidative stress. H2A.Z represses cat-3 gene expression through direct incorporation at cat-3 locus in a SWR1 complex dependent pathway...
May 5, 2018: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29729078/archaeal-dna-on-the-histone-merry-go-round
#13
Sudipta Bhattacharyya, Francesca Mattiroli, Karolin Luger
How did the nucleosome, the fundamental building block of all eukaryotic chromatin, evolve? This central question has been impossible to address because the four core histones that make up the protein core of the nucleosome are so highly conserved in all eukaryotes. With the discovery of small, minimalist histone-like proteins in most known archaea, the likely origin of histones was identified. We recently determined the structure of an archaeal histone-DNA complex, revealing that archaeal DNA topology and protein-DNA interactions are astonishingly similar compared to the eukaryotic nucleosome...
May 4, 2018: FEBS Journal
https://www.readbyqxmd.com/read/29707605/scaling-up-to-study-brca2-the-zeppelin-zebrafish-mutant-reveals-a-role-for-brca2-in-embryonic-development-of-kidney-mesoderm
#14
Bridgette E Drummond, Rebecca A Wingert
Specialized renal epithelial cells known as podocytes are essential components of the filtering structures within the kidney that coordinate the process of removing waste from the bloodstream. Podocyte loss initiates many human kidney diseases as it triggers subsequent damage to the kidney, leading to progressive loss of function that culminates with end stage renal failure. Podocyte morphology, function and gene expression profiles are well conserved between zebrafish and humans, making the former a relevant model to study podocyte development and model kidney diseases...
2018: Cancer Cell & Microenvironment
https://www.readbyqxmd.com/read/29704296/rtt109-dependent-histone-h3-k56-acetylation-and-gene-activity-are-essential-for-the-biological-control-potential-of-beauveria-bassiana
#15
Qing Cai, Juan-Juan Wang, Wei Shao, Sheng-Hua Ying, Ming-Guang Feng
BACKGROUND: Rtt109 is a histone acetyltransferase that catalyzes histone H3K56 acetylation required for genomic stability, DNA damage repair and virulence-related gene activity in yeast-like human pathogens but remains functionally unknown in fungal insect pathogens. This study seeks to elucidate catalytic activity of Rtt109 orthologue and its possible role in sustaining biological control potential of Beauveria bassiana, a fungal entomopathogen. RESULTS: Deletion of rtt109 in B...
April 27, 2018: Pest Management Science
https://www.readbyqxmd.com/read/29698802/histology-guided-proteomic-analysis-to-investigate-the-molecular-profiles-of-clear-cell-renal-cell-carcinoma-grades
#16
Martina Stella, Clizia Chinello, Anna Cazzaniga, Andrew Smith, Manuel Galli, Isabella Piga, Angelica Grasso, Marco Grasso, Marina Del Puppo, Marta Varallo, Giorgio Bovo, Fulvio Magni
Renal Cell Carcinoma (RCC) is the most frequent form of kidney cancer and approximately 80% of cases are defined as clear cell RCC (ccRCC). Among the histopathological factors, tumour grade represents one of the most important parameters to evaluate ccRCC progression. Nonetheless, the molecular processes associated with the grading classification haven't been deeply investigated thus far. Therefore, the aim of this study was to uncover protein alterations associated with different ccRCC grade lesions. Formalin-fixed paraffin-embedded samples from ccRCC patients were analysed by histology-guided MALDI-MSI and shotgun proteomics in order to study the biological processes implicated in ccRCC...
April 23, 2018: Journal of Proteomics
https://www.readbyqxmd.com/read/29694335/mysm1-is-essential-for-maintaining-hematopoietic-stem-cell-hsc-quiescence-and-survival
#17
Yi Huo, Bing-Yi Li, Zhi-Feng Lin, Wei Wang, Xiao-Xia Jiang, Xu Chen, Wen-Jin Xi, An-Gang Yang, Si-Yi Chen, Tao Wang
BACKGROUND Histone H2A deubiquitinase MYSM1 has recently been shown to be essential for hematopoiesis and hematopoietic stem cell (HSC) function in both mice and humans. However, conventional MYSM1 knockouts cause partial embryonic lethality and growth retardation, and it is difficult to convincingly remove the effects of environmental factors on HSC differentiation and function. MATERIAL AND METHODS MYSM1 conditional knockout (cKO) mice were efficiently induced by using the Vav1-cre transgenic system. The Vav-Cre MYSM1 cKO mice were then analyzed to verify the intrinsic role of MYSM1 in hematopoietic cells...
April 25, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29684657/engineering-low-cadmium-rice-through-stress-inducible-expression-of-oxs3-family-member-genes
#18
Changhu Wang, Weili Guo, Xingzhe Cai, Ruyu Li, David W Ow
Cadmium (Cd) as a carcinogen poses a great threat to food security and public health through plant-derived foods such as rice, the staple for nearly half of the world's population. We have previously reported that overexpression of truncated gene fragments derived from the rice genes OsO3L2 and OsO3L3 could reduce Cd accumulation in transgenic rice. However, we did not test the full length genes due to prior work in Arabidopsis where overexpression of these genes caused seedling lethality. Here, we report on limiting the overexpression of OsO3L2 and OsO3L3 through the use of the stress- inducible promoter RD29B...
April 20, 2018: New Biotechnology
https://www.readbyqxmd.com/read/29678836/tumor-suppressor-bap1-is-essential-for-thymic-development-and-proliferative-responses-of-t-lymphocytes
#19
Teresita L Arenzana, Steve Lianoglou, Akiko Seki, Celine Eidenschenk, Tommy Cheung, Dhaya Seshasayee, Thijs Hagenbeek, Arivazhagan Sambandam, Rajkumar Noubade, Ivan Peng, Justin Lesch, Jason DeVoss, Xiumin Wu, Wyne P Lee, Patrick Caplazi, Joshua Webster, Jinfeng Liu, Victoria C Pham, David Arnott, Jennie R Lill, Zora Modrusan, Anwesha Dey, Sascha Rutz
Loss of function of the nuclear deubiquitinating enzyme BRCA1-associated protein-1 (BAP1) is associated with a wide spectrum of cancers. We report that tamoxifen-induced BAP1 deletion in adult mice resulted in severe thymic atrophy. BAP1 was critical for T cell development at several stages. In the thymus, BAP1 was required for progression through the pre-T cell receptor checkpoint. Peripheral T cells lacking BAP1 demonstrated a defect in homeostatic and antigen-driven expansion. Deletion of BAP1 resulted in suppression of E2F target genes and defects in cell cycle progression, which was dependent on the catalytic activity of BAP1, but did not require its interaction with host cell factor-1 (HCF-1)...
April 20, 2018: Science Immunology
https://www.readbyqxmd.com/read/29676825/histone-chaperones-play-crucial-roles-in-maintenance-of-stem-cell-niche-during-plant-root-development
#20
Jing Ma, Yuhao Liu, Wangbin Zhou, Yan Zhu, Aiwu Dong, Wen-Hui Shen
Stem cells in both plant and animal kingdoms reside in a specialized cellular context called stem-cell niche (SCN). SCN integrity is crucial for organism development. Here we show that the H3/H4 histone chaperone CHROMATIN ASSEMBLY FACTOR-1 (CAF-1) and the H2A/H2B histone chaperone NAP1-RELATED PROTEIN1/2 (NRP1/2) play synergistic roles in Arabidopsis root SCN maintenance. Compared to either the m56-1 double mutant deprived of NRP1 and NRP2 or the fas2-4 mutant deprived of CAF-1, the combined m56-1fas2-4 triple mutant displayed a much more severe short-root phenotype...
April 20, 2018: Plant Journal: for Cell and Molecular Biology
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