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Shintaro Yamada, Kazuto Kugou, Da-Qiao Ding, Yurika Fujita, Yasushi Hiraoka, Hiroshi Murakami, Kunihiro Ohta, Takatomi Yamada
Meiotic recombination ensures faithful chromosome segregation and confers genetic diversity to gametes, and thus, is a key DNA-templated reaction not only for sexual reproduction, but also evolution. This recombination is initiated by programmed DNA double strand breaks (DSBs), which are mainly formed at recombination hotspots. As meiotic DSB formation requires multiple proteins, it is regulated by chromatin structure. In particular, DSB occurs in a higher-order chromatin architecture termed "axis-loop", in which many loops protrude from proteinaceous axis...
March 16, 2018: Current Genetics
Antoine Molaro, Janet M Young, Harmit S Malik
Eukaryotic genomes must accomplish both compact packaging for genome stability and inheritance, as well as accessibility for gene expression. They do so using post-translational modifications of four ancient canonical histone proteins (H2A, H2B, H3, and H4) and by deploying histone variants with specialized chromatin functions. Some histone variants are conserved across all eukaryotes, whereas others are lineage-specific. Here, we performed detailed phylogenomic analyses of "short H2A histone" variants found in mammalian genomes...
March 16, 2018: Genome Research
Celine Tasset, Avilash Singh Yadav, Sridevi Sureshkumar, Rupali Singh, Lennard van der Woude, Maxim Nekrasov, David Tremethick, Martijn van Zanten, Sureshkumar Balasubramanian
Ambient temperature affects plant growth and even minor changes can substantially impact crop yields. The underlying mechanisms of temperature perception and response are just beginning to emerge. Chromatin remodeling, via the eviction of the histone variant H2A.Z containing nucleosomes, is a critical component of thermal response in plants. However, the role of histone modifications remains unknown. Here, through a forward genetic screen, we identify POWERDRESS (PWR), a SANT-domain containing protein known to interact with HISTONE DEACETYLASE 9 (HDA9), as a novel factor required for thermomorphogenesis in Arabidopsis thaliana...
March 16, 2018: PLoS Genetics
Jinxu Gao, Adelphe Mfuh, Yuka Amako, Christina M Woo
Many therapeutics elicit cell-type specific polypharmacology that is executed by a network of molecular recognition events between a small molecule and the whole proteome. However, measurement of the structures that underpin the molecular associations between the proteome and even common therapeutics, such as the nonsteroidal anti-inflammatory drugs (NSAIDs), is limited by the inability to map the small molecule interactome. To address this gap, we developed a platform termed small molecule interactome mapping by photoaffinity labeling (SIM-PAL) and applied it to the in cellulo direct characterization of specific NSAID binding sites...
March 15, 2018: Journal of the American Chemical Society
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
Beng Yang, Rongliang Tong, Hua Liu, Jingbang Wu, Diyu Chen, Zhengze Xue, Chaofeng Ding, Lin Zhou, Haiyang Xie, Jian Wu, Shusen Zheng
Intrahepatic cholangiocarcinoma (ICC) is a fatal, malignant tumor of the liver; effective diagnostic biomarkers and therapeutic targets for ICC have not been identified yet. High expression of H2A histone family member Z (H2A.Z) is a high-risk factor for poor prognosis in patients with breast cancer and primary hepatocellular cancer. However, the significance of H2A.Z and its expression in ICC remains unknown. The present study demonstrated that H2A.Z is overexpressed in ICC and expression of H2A.Z correlated with poor prognosis in patients with ICC...
April 2018: International Journal of Oncology
Hyewon Shin, Minzhen He, Zhi Yang, Yong Heui Jeon, Jessica Pfleger, Danish Sayed, Maha Abdellatif
The mechanisms that regulate H2A.Z and its requirement for transcription in differentiated mammalian cells remains ambiguous. In this study, we identified the interaction between the C-terminus of ANP32e and N-terminus of H2A.Z in a yeast two-hybrid screen. Knockdown of ANP32e resulted in proteasomal degradation and nuclear depletion of H2A.Z or of a chimeric green florescence protein fused to its N-terminus. This effect was reversed by inhibition of protein phosphatase 2A (PP2A) and, conversely, reproduced by overexpression of its catalytic subunit...
March 7, 2018: Biochimica et Biophysica Acta
Macarena Guijo, María Ceballos-Chávez, Elena Gómez-Marín, Laura Basurto-Cayuela, José C Reyes
Tudor domain containing protein 9 (TDRD9) is a RNA helicase normally expressed in the germline, where it is involved in the biosynthesis of PIWI-interacting RNAs (piRNAs). Here, we show that TDRD9 is highly expressed in a subset of non-small cell lung carcinomas and derived cell lines by hypomethylation of its CpG island. Furthermore, TDRD9 expression is associated with poor prognosis in lung adenocarcinoma. We find that downregulation of TDRD9 expression in TDRD9-positive cell lines causes a decrease in cell proliferation, S-phase cell cycle arrest, and apoptosis...
February 9, 2018: Oncotarget
Almesh Kadakol, Vajir Malek, Santosh Kumar Goru, Anuradha Pandey, Anil Bhanudas Gaikwad
OBJECTIVES: Although cardioprotective effects of telmisartan are well explored, its effects on epigenetic alterations associated with type 2 diabetic (T2D) cardiomyopathy remain unmapped. Thus, the present study was designed to evaluate the potential of esculetin and telmisartan combination to reverse histone posttranslational modifications (PTMs) in curbing T2D cardiomyopathy. MATERIALS AND METHODS: T2D was induced by high-fat diet feeding along with low dose of streptozotocin (35 mg/kg, I...
September 2017: Indian Journal of Pharmacology
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
Laura L McCullough, Zaily Connell, Hua Xin, Vasily M Studitsky, Alexey V Feofanov, Maria E Valieva, Tim Formosa
The essential histone chaperone FAcilitates Chromatin Transcription (FACT) promotes both nucleosome assembly and disassembly. FACT is a heterodimer of Spt16 with either SSRP1 or Pob3, differing primarily by the presence of a high-mobility group B (HMGB) DNA-binding domain furnished only by SSRP1. Yeast FACT lacks the intrinsic HMGB domain found in SSRP1-based homologs such as human FACT, but yeast FACT activity is supported by Nhp6, which is a freestanding, single HMGB domain protein. The importance of histone binding by FACT domains has been established, but the roles of DNA binding activity remain poorly understood...
March 7, 2018: Journal of Biological Chemistry
Shiqing Zhou, Yanghai Yu, Weiqiu Zhang, Xiaoyang Meng, Jinming Luo, Lin Deng, Zhou Shi, John C Crittenden
Advanced oxidation processes (AOPs) have been widely used for the destruction of organic contaminants in the aqueous phase. In this study, we introduce an AOP on activated peroxymonosulfate (PMS) by using ascorbic acid (H2A) to generate sulfate radicals (SO4•-). Sulfate radicals, hydroxyl radicals (HO•) and ascorbyl radicals (A•-) were found using electron spin resonance (ESR). But we found A•- is negligible in the degradation of microcystin-LR (MCLR) due to its low reactivity. We developed a first-principles kinetic model to simulate the MCLR degradation and predict the radical concentrations...
March 7, 2018: Environmental Science & Technology
Zenab F Mchaourab, Andrea A Perreault, Bryan J Venters
The human K562 chronic myeloid leukemia cell line has long served as an experimental paradigm for functional genomic studies. To systematically and functionally annotate the human genome, the ENCODE consortium generated hundreds of functional genomic data sets, such as chromatin immunoprecipitation coupled to sequencing (ChIP-seq). While ChIP-seq analyses have provided tremendous insights into gene regulation, spatiotemporal insights were limited by a resolution of several hundred base pairs. ChIP-exonuclease (ChIP-exo) is a refined version of ChIP-seq that overcomes this limitation by providing higher precision mapping of protein-DNA interactions...
March 6, 2018: Scientific Data
Jia-Bin Li, Yun-Kun Qi, Qiao-Qiao He, Hua-Song Ai, San-Ling Liu, Jia-Xing Wang, Ji-Shen Zheng, Lei Liu, Changlin Tian
This corrects the article DOI: 10.1038/cr.2017.157.
February 2018: Cell Research
Chiahao Tsui, Carla Inouye, Michaella Levy, Andrew Lu, Laurence Florens, Michael P Washburn, Robert Tjian
Eukaryotic gene regulation is a complex process, often coordinated by the action of tens to hundreds of proteins. Although previous biochemical studies have identified many components of the basal machinery and various ancillary factors involved in gene regulation, numerous gene-specific regulators remain undiscovered. To comprehensively survey the proteome directing gene expression at a specific genomic locus of interest, we developed an in vitro nuclease-deficient Cas9 (dCas9)-targeted chromatin-based purification strategy, called "CLASP" (Cas9 locus-associated proteome), to identify and functionally test associated gene-regulatory factors...
March 5, 2018: Proceedings of the National Academy of Sciences of the United States of America
Christina Wilms, Ioanna Krikki, Adelheid Hainzl, Sonja Kilo, Marius Alupei, Evgenia Makrantonaki, Maximilian Wagner, Carsten M Kroeger, Titus Josef Brinker, Martina Gatzka
Development and homeostasis of the epidermis are governed by a complex network of sequence-specific transcription factors and epigenetic modifiers cooperatively regulating the subtle balance of progenitor cell self-renewal and terminal differentiation. To investigate the role of histone H2A deubiquitinase 2A-DUB/Mysm1 in the skin, we systematically analyzed expression, developmental functions, and potential interactions of this epigenetic regulator using Mysm1-deficient mice and skin-derived epidermal cells...
February 28, 2018: International Journal of Molecular Sciences
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
Shannel R Adams, So Maezawa, Kris G Alavattam, Hironori Abe, Akihiko Sakashita, Megan Shroder, Tyler J Broering, Julie Sroga Rios, Michael A Thomas, Xinhua Lin, Carolyn M Price, Artem Barski, Paul R Andreassen, Satoshi H Namekawa
The sex chromosomes are enriched with germline genes that are activated during the late stages of spermatogenesis. Due to meiotic sex chromosome inactivation (MSCI), these sex chromosome-linked genes must escape silencing for activation in spermatids, thereby ensuring their functions for male reproduction. RNF8, a DNA damage response protein, and SCML2, a germline-specific Polycomb protein, are two major, known regulators of this process. Here, we show that RNF8 and SCML2 cooperate to regulate ubiquitination during meiosis, an early step to establish active histone modifications for subsequent gene activation...
February 20, 2018: PLoS Genetics
Patrick J Murphy, Shan Fu Wu, Cody R James, Candice L Wike, Bradley R Cairns
The fate and function of epigenetic marks during the germline-to-embryo transition is a key issue in developmental biology, with relevance to stem cell programming and transgenerational inheritance. In zebrafish, DNA methylation patterns are programmed in transcriptionally quiescent cleavage embryos; paternally inherited patterns are maintained, whereas maternal patterns are reprogrammed to match the paternal. Here, we provide the mechanism by demonstrating that "Placeholder" nucleosomes, containing histone H2A variant H2A...
February 9, 2018: Cell
Xin-Ran Li, Joyita Deb, S Vinod Kumar, Lars Østergaard
Plants respond to diurnal and seasonal changes in temperature by reprogramming vital developmental pathways. Understanding the molecular mechanisms that define environmental modulation of plant growth and reproduction is critical in the context of climate change that threatens crop yield worldwide. Here, we report that elevated temperature accelerates fruit dehiscence in members of the Brassicaceae family including the model plant Arabidopsis thaliana and important crop species. Arabidopsis fruit development is controlled by a network of interacting regulatory genes...
February 7, 2018: Molecular Plant
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