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Histone H4

Qing Cai, Sen-Miao Tong, Wei Shao, Sheng-Hua Ying, Ming-Guang Feng
Histone acetyltransferases (HATs) and deacetylases (HDACs) maintain dynamics of lysine acetylation/deacetylation on histones and non-histone substrates involved in gene regulation and cellular events. Hos2 is a class I HDAC that deacetylates unique histone H4-K16 site in yeasts. Here, we report that orthologous Hos2 deacetylates H4-K16 and is also involved in the acetylation of histone H3-K56 and the phosphorylation of histone H2A-S129 and cyclin-dependent kinase 1 CDK1-Y15 in Beauveria bassiana, a filamentous fungal insect pathogen...
March 15, 2018: Cellular Microbiology
Geetha S Hewawasam, Karthik Dhatchinamoorthy, Mark Mattingly, Chris Seidel, Jennifer L Gerton
Correct localization of the centromeric histone variant CenH3/CENP-A/Cse4 is an important part of faithful chromosome segregation. Mislocalization of CenH3 could affect chromosome segregation, DNA replication and transcription. CENP-A is often overexpressed and mislocalized in cancer genomes, but the underlying mechanisms are not understood. One major regulator of Cse4 deposition is Psh1, an E3 ubiquitin ligase that controls levels of Cse4 to prevent deposition into non-centromeric regions. We present evidence that Chromatin assembly factor-1 (CAF-1), an evolutionarily conserved histone H3/H4 chaperone with subunits shown previously to interact with CenH3 in flies and human cells, regulates Cse4 deposition in budding yeast...
March 7, 2018: Nucleic Acids Research
Hyungwoo Cho, Dok Hyun Yoon, Kyu-Pyo Kim, Kyun-Seop Bae, Won Seog Kim, Hyeon-Seok Eom, Jin Seok Kim, Jung Yong Hong, Seok Jin Kim, Hyewon Lee, Soo-Jeong Kim, Cheolwon Suh
Background The objective of this study was to assess the safety, dose-limiting toxicities (DLTs), maximum tolerated dose (MTD), pharmacokinetics, and anti-tumor efficacy of CKD-581, a novel pan-histone deacetylase inhibitor, in patients with lymphoma or multiple myeloma (MM) refractory to standard therapy. Methods In this phase I study, CKD-581 was intravenously administered on days 1, 8, and 15 of a 28-day cycle. A standard 3 + 3 cohort design was used to determine the MTD. Acetylated histones H3 and H4 in peripheral blood mononuclear cells were measured for pharmacodynamic assessment in a subpopulation of patients...
March 9, 2018: Investigational New Drugs
Raphaël Coscas, Sebastien Dupont, Sacha Mussot, Liliane Louedec, Harry Etienne, Marion Morvan, Gilles Chiocchia, Ziad Massy, Marie-Paule Jacob, Jean-Baptiste Michel
BACKGROUND: Recent evidence suggests that adaptive immunity develops during abdominal aortic aneurysm evolution. Uncertainties remain about the antigens implicated and their role in inducing rupture. Because antigens from the extracellular matrix (ECM) have been suspected, the aim of this experimental study was to characterize the role of adaptive immunity directed against antigens from the aortic ECM. METHODS: In a first step, an experimental model of abdominal aortic aneurysm rupture based on adaptive immunity against the ECM was developed and characterized...
March 5, 2018: Journal of Vascular Surgery
Hironori Funabiki, Christopher Jenness, Christian Zierhut
The majority of eukaryotic chromosomal DNA exists in the form of nucleosomes, where ∼147 bp DNA wraps around histone hetero-octamers, composed of histone H3, H4, H2A, and H2B. Despite their obvious importance in DNA compaction and accessibility, studying their specific roles, such as regulation of mitotic progression, in a physiological environment is associated with critical caveats because of their major contributions in transcriptional control. Through establishing a method to deplete endogenous histones H3 and H4 from frog egg extracts and complementing their functions using recombinant nucleosome arrays, we are now able to analyze their roles in mitotic progression without affecting overall transcriptomic profiles...
March 7, 2018: Cold Spring Harbor Symposia on Quantitative Biology
Tinchou Li, Mingcheng Lee, Fuming Tsai, Yunhsiang Chen, Yiyin Lin, Maoliang Chen
BACKGROUND: Based on accumulating evidence, the regulation of protein expression by antipsychotic drugs (APDs) might be closely related to the control of psychotic symptoms when these drugs are used to treat mental disorders. The low quantity of nuclear proteins in the cell hinders their detection because signal for rare proteins are masked in most proteomic detection systems. METHODS: Nuclear proteins fractionated from APD-treated B35 cells were labeled with iTRAQ and detected by LC/MS/MS to investigate APD-induced alterations in nuclear protein expression...
March 7, 2018: BMC Pharmacology & Toxicology
Yan Yang, Kai Xue, Zhi Li, Wei Zheng, Weijie Dong, Jiazhe Song, Shijie Sun, Tonghui Ma, Wenzhe Li
Overexpression of c-Myc is involved in the tumorigenesis of B-lineage acute lymphoblastic leukemia (B‑ALL), but the mechanism is not well understood. In the present study, a c‑Myc‑knockdown model (Raji‑KD) was established using Raji cells, and it was indicated that c‑Myc regulates the expression of genes associated with cell cycle progression in G2/M‑phase, cyclin D kinase (CDK)1 and cyclin B1, by modulating 60 kDa Tat‑interactive protein (TIP60)/males absent on the first (MOF)‑mediated histone H4 acetylation (AcH4), which was then completely restored by re‑introduction of the c‑Myc gene into the Raji‑KD cells...
February 28, 2018: International Journal of Molecular Medicine
Lichun Sun, Quanyong He, Cheguo Tsai, Jun Lei, Jing Chen, Lily Vienna Makcey, David H Coy
Small cell lung cancer (SCLC) is a malignant human cancer and patients have very limited benefit from traditional anticancer treatments, with a poor five-year survival rate being 10% less. In present study, we observed that Notch signalling activation induced SCLC cell growth suppression via overexpressing Notch active fragments (ICN1, ICN2, ICN3 and ICN4), implying its tumor suppressive role. The histone deacetylase (HDAC) inhibitors also displayed their suppressive effects. Valproic acid (VPA) as a HDAC inhibitor was found to suppress SCLC cell growth and cell cycle arrest at phase G1, and observed to decrease HDAC4 and increase acetylation of histone H4 (AcH4) while activating Notch signalling with an increase of Notch1, Notch target gene HES1 and p21...
2018: American Journal of Translational Research
Boya Zhang, Xianzhen Chen, Qiang Zhou, Yinjing Song, Siyuan Sun, Hao Cheng
OBJECTIVE: Human papillomavirus (HPV) is the most common sexually transmitted agent in the world. HPV6b is a low-risk type of HPVs that causes benign verrucous hyperplastic lesions of the skin and anal genital mucosa. Previous research has indicated that HPV genotype 6 is sometimes associated with high-grade lesions and anal cancer. The pathogenesis of low-risk HPV infection and its relationship to high-risk HPV is not clear at present. The E7 protein, which is encoded by HPV early -expressing genes, plays an important role in HPV infection...
March 1, 2018: Gene
David Corujo, Marcus Buschbeck
Histone variants are chromatin components that replace replication-coupled histones in a fraction of nucleosomes and confer particular characteristics to chromatin. H2A variants represent the most numerous and diverse group among histone protein families. In the nucleosomal structure, H2A-H2B dimers can be removed and exchanged more easily than the stable H3-H4 core. The unstructured N-terminal histone tails of all histones, but also the C-terminal tails of H2A histones protrude out of the compact structure of the nucleosome core...
February 27, 2018: Cancers
Meraj A Khan, Lijy M Philip, Guillaume Cheung, Shawn Vadakepeedika, Hartmut Grasemann, Neil Sweezey, Nades Palaniyar
Neutrophils migrating from the blood (pH 7.35-7.45) into the surrounding tissues encounter changes in extracellular pH (pHe ) conditions. Upon activation of NADPH oxidase 2 (Nox), neutrophils generate large amounts of H+ ions reducing the intracellular pH (pHi ). Nevertheless, how extracellular pH regulates neutrophil extracellular trap (NET) formation (NETosis) is not clearly established. We hypothesized that increasing pH increases Nox-mediated production of reactive oxygen species (ROS) and neutrophil protease activity, stimulating NETosis...
2018: Frontiers in Medicine
Rashmi Dahiya, Krishnamurthy Natarajan
TAF6, bearing histone H4-like histone fold domain, is a subunit of the core TAF module in TFIID and SAGA transcriptional regulatory complexes. We isolated and characterized several yeast TAF6 mutants bearing amino acid substitutions in the histone fold domain, the middle region or the HEAT repeat domain. The TAF6 mutants were highly defective for transcriptional activation by the Gcn4 and Gal4 activators. Chromatin immunoprecipitation assays showed that the TAF6-HFD and the TAF6-HEAT domain mutations independently abrogated the promoter occupancy of TFIID and SAGA complex in vivo...
February 27, 2018: FEBS Journal
Shalaka Chitale, Holger Richly
The integrity of the genome is maintained by specific DNA repair pathways. The main pathway removing DNA lesions induced by exposure to UV light is nucleotide excision repair (NER). The DNA damage response at chromatin is accompanied by the recruitment of DNA repair factors to the lesion site and the deposition of specific histone marks. The function of these histone marks in NER stays for the most part elusive. We have recently reported that the methyltransferase MMSET catalyzes the dimethylation of histone H4 at lysine 20 (H4K20me2) at the lesion site...
February 26, 2018: Nucleus
Katie L Bales, Lara Ianov, Andrew J Kennedy, J David Sweatt, Alecia K Gross
Purpose: Epigenetic and transcriptional mechanisms have been shown to contribute to long-lasting functional changes in adult neurons. The purpose of this study was to identify any such modifications in diseased retinal tissues from a mouse model of rhodopsin mutation-associated autosomal dominant retinitis pigmentosa (ADRP), Q344X, relative to age-matched wild-type (WT) controls. Methods: We performed RNA sequencing (RNA-seq) at poly(A) selected RNA to profile the transcriptional patterns in 3-week-old ADRP mouse model rhodopsin Q344X compared to WT controls...
2018: Molecular Vision
Jiamei Lin, Shengqiang Wang, Yunlin Feng, Weihong Zhao, Weilu Zhao, Foquan Luo, Namin Feng
Propofol is widely used in clinical practice, including non-obstetric surgery in pregnant women. Previously, we found that propofol anaesthesia in maternal rats during the third trimester (E18) caused learning and memory impairment to the offspring rats, but how about the exposure during early pregnancy and the underlying mechanisms? Histone acetylation plays an important role in synaptic plasticity. In this study, propofol was administered to the pregnant rats in the early pregnancy (E7). The learning and memory function of the offspring were tested by Morris water maze (MWM) test on post-natal day 30...
February 20, 2018: Journal of Cellular and Molecular Medicine
Svetlana V Baranova, Pavel S Dmitrenok, Anastasiya D Zubkova, Nikita V Ivanisenko, Elena S Odintsova, Valentina N Buneva, Georgy A Nevinsky
Histones and their posttranslational modified forms play pivotal roles in chromatin functioning and gene transcription. Also, histones are harmful when they enter the intercellular space; their administration to animals results in systemic inflammatory and toxic responses. Autoantibodies having enzymatic activities (abzymes) are the specific feature of several autoimmune and viral diseases. Electrophoretically homogeneous IgGs containing no canonical proteases were purified from sera of HIV-infected patients by using several affinity chromatographies...
February 19, 2018: Journal of Molecular Recognition: JMR
M K Sannigrahi, Rajni Sharma, Varinder Singh, Naresh K Panda, Vidya Rattan, Madhu Khullar
INTRODUCTION: Epigenetic modifications have been reported to play an important role in regulating gene expression and these modifications become critical when they have a role in controlling another important layer of epigenetic regulation namely microRNAs. In the present study, we have identified the microRNAs that may be regulated by promoter DNA methylation and histone acetylation in Human papilloma virus-positive head and neck squamous cell carcinoma. METHODOLOGY: HPV-negative cell line (UPCI:SCC-116) and HPV-16 +ve cell line (UPCI:SCC-090) were treated with methylation inhibitor (5-aza-2'-deoxycytidine, AZA) and acetylation inhibitor (Trichostatin-A, TSA), followed by micro-array analysis...
February 17, 2018: Molecular and Cellular Biochemistry
Jie-Fei Miao, Yan-Fu Peng, Shi Chen, Wei-Jie Gao, Qiu-Xing Yang, Peng Zhu, Jing Guo, Jinhua Tao, Lin Luo, Yanan Zhang, Yong Ling
This study aims to design and synthesize a novel harmine derivative N-(4-(hydroxycarbamoyl) benzyl)-1-(4-methoxyphenyl)-9H-pyrido [3,4-b]indole-3-carboxamide (HBC) as histone deacetylase (HDAC) inhibitor, and evaluate its antitumor activities and anti-metastasis mechanism. HBC not only exerted significant ant-proliferation activity against five human cancer cell lines, especially for HepG2 cell with an IC50 value of 2.21μM, which is nearly three-fold lower than SAHA (IC50 = 6.26µM), but also showed selective HDAC1/6 inhibitory effects in vitro...
February 8, 2018: European Journal of Pharmacology
Samantha B Shelton, Nakul M Shah, Nathan S Abell, Sravan K Devanathan, Marvin Mercado, Blerta Xhemalçe
RNAP II switching from the paused to the productive transcription elongation state is a pivotal regulatory step that requires specific phosphorylations catalyzed by the P-TEFb kinase. Nucleosolic P-TEFb activity is inhibited by its interaction with the ribonuclear protein complex built around the 7SK small nuclear RNA (7SK snRNP). MePCE is the RNA methyltransferase that methylates and stabilizes 7SK in the nucleosol. Here, we report that MePCE also binds chromatin through the histone H4 tail to serve as a P-TEFb activator at specific genes important for cellular identity...
February 6, 2018: Cell Reports
Kana Tanabe, Jiaan Liu, Daiki Kato, Hitoshi Kurumizaka, Kenzo Yamatsugu, Motomu Kanai, Shigehiro A Kawashima
Chromatin structure and gene expression are dynamically regulated by posttranslational modifications of histones. Recent advance in mass spectrometry has identified novel types of lysine acylations, such as butyrylation and malonylation, whose functions and regulations are likely different from those of acetylation. Sirtuins, nicotinamide adenine dinucleotide (NAD+)-dependent histone deacetylases, catalyze various deacylations. However, it is poorly understood how distinct sirtuins regulate the histone acylation states of nucleosomes that have many lysine residues...
February 8, 2018: Scientific Reports
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