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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
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
Nguyen Hoai Nguyen, Jong-Joo Cheong
Transcripts of the Arabidopsis transcription factor gene, AtMYB44, accumulate rapidly to mediate a tolerance mechanism in response to salt stress. The AtMYB44 promoter is activated by salt stress, as illustrated in AtMYB44pro::GUS transgenic plants. Chromatin immunoprecipitation (ChIP) assays revealed that RNA polymerases were enriched on the AtMYB44 gene, especially on TSS-proximal regions, and nucleosome density was markedly reduced in the AtMYB44 gene-body region in response to salt stress. In addition, H2A...
April 9, 2018: Biochemical and Biophysical Research Communications
Sebastian Eustermann, Kevin Schall, Dirk Kostrewa, Kristina Lakomek, Mike Strauss, Manuela Moldt, Karl-Peter Hopfner
In the eukaryotic nucleus, DNA is packaged in the form of nucleosomes, each of which comprises about 147 base pairs of DNA wrapped around a histone protein octamer. The position and histone composition of nucleosomes is governed by ATP-dependent chromatin remodellers1-3 such as the 15-subunit INO80 complex 4 . INO80 regulates gene expression, DNA repair and replication by sliding nucleosomes, the exchange of histone H2A.Z with H2A, and the positioning of + 1 and -1 nucleosomes at promoter DNA5-8 . The structures and mechanisms of these remodelling reactions are currently unknown...
April 11, 2018: Nature
Felix Wojcik, Geoffrey P Dann, Leslie Y Beh, Galia T Debelouchina, Raphael Hofmann, Tom W Muir
Ubiquitylation of histone H2B at lysine residue 120 (H2BK120ub) is a prominent histone posttranslational modification (PTM) associated with the actively transcribed genome. Although H2BK120ub triggers several critical downstream histone modification pathways and changes in chromatin structure, less is known about the regulation of the ubiquitylation reaction itself, in particular with respect to the modification status of the chromatin substrate. Here we employ an unbiased library screening approach to profile the impact of pre-existing chromatin modifications on de novo ubiquitylation of H2BK120 by the cognate human E2:E3 ligase pair, UBE2A:RNF20/40...
April 11, 2018: Nature Communications
Xiaozhuan Dai, Youhuang Bai, Lihua Zhao, Xianying Dou, Yanhui Liu, Lulu Wang, Yi Li, Weimin Li, Yanan Hui, Xinyu Huang, Zonghua Wang, Yuan Qin
No abstract text is available yet for this article.
April 2, 2018: Molecular Plant
Ángeles Gómez-Zambrano, Pedro Crevillén, José M Franco-Zorrilla, Juan A López, Jordi Moreno-Romero, Pawel Roszak, Juan Santos-González, Silvia Jurado, Jesús Vázquez, Claudia Köhler, Roberto Solano, Manuel Piñeiro, José A Jarillo
Deposition of the H2A.Z histone variant by the SWR1 complex (SWR1-C) in regulatory regions of specific loci modulates transcription. Characterization of Arabidopsis thaliana mutations in homologs of the yeast SWR1-C has revealed a role for H2A.Z exchange in a variety of developmental processes; nevertheless, the exact composition of the plant SWR1-C and how it is recruited to target genes remains to be established. Here we show that SWC4, the Arabidopsis homolog of the yeast SANT domain protein Swc4/Eaf2, is a DNA-binding protein that interacts with SWR1-C subunits...
March 28, 2018: Molecular Plant
Douglas Maya Miles, Xenia Peñate, Trinidad Sanmartín Olmo, Frederic Jourquin, Maria Cruz Muñoz Centeno, Manuel Mendoza, Marie-Noelle Simon, Sebastian Chavez, Vincent Geli
Whole-genome duplications (WGDs) have played a central role in the evolution of genomes and constitute an important source of genome instability in cancer. Here, we show in Saccharomyces cerevisiae that abnormal accumulations of histones are sufficient to induce WGDs. Our results link these WGDs to a reduced incorporation of the histone variant H2A.Z to chromatin. Moreover, we show that high levels of histones promote Swe1WEE1 stabilisation thereby triggering the phosphorylation and inhibition of Cdc28CDK1 through a mechanism different of the canonical DNA damage response...
March 27, 2018: ELife
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
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 2018: PLoS Genetics
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...
May 2018: Biochimica et Biophysica Acta
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
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
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 22, 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...
April 2, 2018: Molecular Plant
Chih-Chao Hsu, Jiejun Shi, Chao Yuan, Dan Zhao, Shiming Jiang, Jie Lyu, Xiaolu Wang, Haitao Li, Hong Wen, Wei Li, Xiaobing Shi
Histone acetylation is associated with active transcription in eukaryotic cells. It helps to open up the chromatin by neutralizing the positive charge of histone lysine residues and providing binding platforms for "reader" proteins. The bromodomain (BRD) has long been thought to be the sole protein module that recognizes acetylated histones. Recently, we identified the YEATS domain of AF9 (ALL1 fused gene from chromosome 9) as a novel acetyl-lysine-binding module and showed that the ENL (eleven-nineteen leukemia) YEATS domain is an essential acetyl-histone reader in acute myeloid leukemias...
January 1, 2018: Genes & Development
Răzvan V Chereji, Srinivas Ramachandran, Terri D Bryson, Steven Henikoff
We developed a chemical cleavage method that releases single nucleosome dyad-containing fragments, allowing us to precisely map both single nucleosomes and linkers with high accuracy genome-wide in yeast. Our single nucleosome positioning data reveal that nucleosomes occupy preferred positions that differ by integral multiples of the DNA helical repeat. By comparing nucleosome dyad positioning maps to existing genomic and transcriptomic data, we evaluated the contributions of sequence, transcription, and histones H1 and H2A...
February 9, 2018: Genome Biology
Der-Fen Suen, Wolfgang Schmidt
Phenotypic plasticity is dependent on the correct interpretation of environmental cues. We recently showed that the deubiquitinase OTU5 is required for orchestrating internal and external signals, tuning the morphogenesis of epidermal cells to the prevailing conditions. Homozygous otu5 mutants developed long and dense root hairs, resembling phosphate-deficient plants. The phenotype of otu5 plants was similar to that of arp6 plants, which carries a mutation that compromises the deposition of H2A.Z. Homozygous otu5 arp6 double mutants exhibited a synergistic phenotype, suggesting that the two mutations are functionally related...
February 2, 2018: Plant Signaling & Behavior
Gilda Stefanelli, Amber B Azam, Brandon J Walters, Mark A Brimble, Caroline P Gettens, Pascale Bouchard-Cannon, Hai-Ying M Cheng, Andrew M Davidoff, Klotilda Narkaj, Jeremy J Day, Andrew J Kennedy, Iva B Zovkic
Histone variants were recently discovered to regulate neural plasticity, with H2A.Z emerging as a memory suppressor. Using whole-genome sequencing of the mouse hippocampus, we show that basal H2A.Z occupancy is positively associated with steady-state transcription, whereas learning-induced H2A.Z removal is associated with learning-induced gene expression. AAV-mediated H2A.Z depletion enhanced fear memory and resulted in gene-specific alterations of learning-induced transcription, reinforcing the role of H2A...
January 30, 2018: Cell Reports
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