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Linchang Dai, Xiaoyan Xie, Zheng Zhou
H2A.Bbd, the most divergent histone variant among all known H2A type histones, is involved in gene transcription, spermiogenesis, DNA replication and RNA splicing. Incorporation of H2A.Bbd-H2B dimer, a fundamental unit of H2A.Bbd nucleosome, modulate structures of nucleosome or chromatin, but the underlying mechanism remains elusive. Here we determined a crystal structure of H2A.Bbd-H2B dimer at 2.6 Å resolution. Although the H2A.Bbd-H2B dimer structure largely resembles that of H2A-H2B, substitution of H2A αC helix residues by H2A...
September 10, 2018: Biochemical and Biophysical Research Communications
Yihao Wang, Yang Chen, Yao Zhang, Wei Wei, Yanchang Li, Tao Zhang, Fuchu He, Yue Gao, Ping Xu
Although 5 years of the missing proteins (MPs) study have been completed, searching for MPs remains one of the core missions of the Chromosome-Centric Human Proteome Project (C-HPP). Following the next-50-MPs challenge of the C-HPP, we have focused on the testis-enriched MPs by various strategies since 2015. On the basis of the theoretical analysis of MPs (2017-01, neXtProt) using multiprotease digestion, we found that nonconventional proteases (e.g. LysargiNase, GluC) could improve the peptide diversity and sequence coverage compared with Trypsin...
December 1, 2017: Journal of Proteome Research
Ciro Rivera-Casas, Rodrigo González-Romero, Ángel Vizoso-Vazquez, Manjinder S Cheema, M Esperanza Cerdán, Josefina Méndez, Juan Ausió, Jose M Eirin-Lopez
Histones are the fundamental constituents of the eukaryotic chromatin, facilitating the physical organization of DNA in chromosomes and participating in the regulation of its metabolism. The H2A family displays the largest number of variants among core histones, including the renowned H2A.X, macroH2A, H2A.B (Bbd), and H2A.Z. This latter variant is especially interesting because of its regulatory role and its differentiation into 2 functionally divergent variants (H2A.Z.1 and H2A.Z.2), further specializing the structure and function of vertebrate chromatin...
October 2016: Biochemistry and Cell Biology
Yasuhiro Arimura, Hiroshi Kimura, Takashi Oda, Koichi Sato, Akihisa Osakabe, Hiroaki Tachiwana, Yuko Sato, Yasuha Kinugasa, Tsuyoshi Ikura, Masaaki Sugiyama, Mamoru Sato, Hitoshi Kurumizaka
No abstract text is available yet for this article.
2015: Scientific Reports
B J Wu, F L Dong, X S Ma, X G Wang, F Lin, H L Liu
Epigenetic modifications of the genome, such as histone H2A variants, ensure appropriate gene activation or silencing during oogenesis and preimplantation embryo development. We examined global localization and expression of the histone H2A variants, including H2A.Bbd, H2A.Z and H2A.X, during mouse oogenesis and preimplantation embryo development. Immunocytochemistry with specific antibodies against various histone H2A variants showed their localization and changes during oogenesis and preimplantation development...
2014: Genetics and Molecular Research: GMR
Viola Sansoni, Corella S Casas-Delucchi, Malini Rajan, Andreas Schmidt, Clemens Bönisch, Andreas W Thomae, Martin S Staege, Sandra B Hake, M Cristina Cardoso, Axel Imhof
Histone variants play an important role in shaping the mammalian epigenome and their aberrant expression is frequently observed in several types of cancer. However, the mechanisms that mediate their function and the composition of the variant-containing chromatin are still largely unknown. A proteomic interrogation of chromatin containing the different H2A variants macroH2A.1.2, H2A.Bbd and H2A revealed a strikingly different protein composition. Gene ontology analysis reveals a strong enrichment of splicing factors as well as components of the mammalian replisome in H2A...
June 2014: Nucleic Acids Research
Yasuhiro Arimura, Hiroshi Kimura, Takashi Oda, Koichi Sato, Akihisa Osakabe, Hiroaki Tachiwana, Yuko Sato, Yasuha Kinugasa, Tsuyoshi Ikura, Masaaki Sugiyama, Mamoru Sato, Hitoshi Kurumizaka
Human histone H2A.B (formerly H2A.Bbd), a non-allelic H2A variant, exchanges rapidly as compared to canonical H2A, and preferentially associates with actively transcribed genes. We found that H2A.B transiently accumulated at DNA replication and repair foci in living cells. To explore the biochemical function of H2A.B, we performed nucleosome reconstitution analyses using various lengths of DNA. Two types of H2A.B nucleosomes, octasome and hexasome, were formed with 116, 124, or 130 base pairs (bp) of DNA, and only the octasome was formed with 136 or 146 bp DNA...
2013: Scientific Reports
Maxim Nekrasov, Tatiana A Soboleva, Cameron Jack, David J Tremethick
Considerable attention has been given to the understanding of how nucleosomes are altered or removed from the transcription start site of RNA polymerase II genes to enable transcription to proceed. This has led to the view that for transcriptional activation to occur, the transcription start site (TSS) must become depleted of nucleosomes. However, we have shown that this is not the case with different unstable histone H2A variant-containing nucleosomes occupying the TSS under different physiological settings...
November 2013: Nucleus
Elena S Ioudinkova, Ana Barat, Andrey Pichugin, Elena Markova, Ilya Sklyar, Iryna Pirozhkova, Chloe Robin, Marc Lipinski, Vasily Ogryzko, Yegor S Vassetzky, Sergey V Razin
BACKGROUND: It becomes increasingly evident that nuclesomes are far from being identical to each other. This nucleosome diversity is due partially to the existence of histone variants encoded by separate genes. Among the known histone variants the less characterized are H2A.Bbd and different forms of macroH2A. This is especially true in the case of H2A.Bbd as there are still no commercially available antibodies specific to H2A.Bbd that can be used for chromatin immunoprecipitation (ChIP)...
2012: PloS One
Michael Y Tolstorukov, Joseph A Goldman, Cristele Gilbert, Vasily Ogryzko, Robert E Kingston, Peter J Park
Variation in chromatin composition and organization often reflects differences in genome function. Histone variants, for example, replace canonical histones to contribute to regulation of numerous nuclear processes including transcription, DNA repair, and chromosome segregation. Here we focus on H2A.Bbd, a rapidly evolving variant found in mammals but not in invertebrates. We report that in human cells, nucleosomes bearing H2A.Bbd form unconventional chromatin structures enriched within actively transcribed genes and characterized by shorter DNA protection and nucleosome spacing...
August 24, 2012: Molecular Cell
Manu Shubhdarshan Shukla, Sajad Hussain Syed, Damien Goutte-Gattat, John Lalith Charles Richard, Fabien Montel, Ali Hamiche, Andrew Travers, Cendrine Faivre-Moskalenko, Jan Bednar, Jeffrey J Hayes, Dimitar Angelov, Stefan Dimitrov
Histone variants within the H2A family show high divergences in their C-terminal regions. In this work, we have studied how these divergences and in particular, how a part of the H2A COOH-terminus, the docking domain, is implicated in both structural and functional properties of the nucleosome. Using biochemical methods in combination with Atomic Force Microscopy and Electron Cryo-Microscopy, we show that the H2A-docking domain is a key structural feature within the nucleosome. Deletion of this domain or replacement with the incomplete docking domain from the variant H2A...
April 2011: Nucleic Acids Research
Toyotaka Ishibashi, Andra Li, José M Eirín-López, Ming Zhao, Kristal Missiaen, D Wade Abbott, Marvin Meistrich, Michael J Hendzel, Juan Ausió
Despite the identification of H2A.Bbd as a new vertebrate-specific replacement histone variant several years ago, and despite the many in vitro structural characterizations using reconstituted chromatin complexes consisting of this variant, the existence of H2A.Bbd in the cell and its location has remained elusive. Here, we report that the native form of this variant is present in highly advanced spermiogenic fractions of mammalian testis at the time when histones are highly acetylated and being replaced by protamines...
April 2010: Nucleic Acids Research
Fabien Montel, Hervé Menoni, Martin Castelnovo, Jan Bednar, Stefan Dimitrov, Dimitar Angelov, Cendrine Faivre-Moskalenko
Chromatin organization and dynamics is studied at scales ranging from single nucleosome to nucleosomal array by using a unique combination of biochemical assays, single molecule imaging technique, and numerical modeling. We show that a subtle modification in the nucleosome structure induced by the histone variant H2A.Bbd drastically modifies the higher order organization of the nucleosomal arrays. Importantly, as directly visualized by atomic force microscopy, conventional H2A nucleosomal arrays exhibit specific local organization, in contrast to H2A...
July 22, 2009: Biophysical Journal
Lydia Ferguson, Peter J I Ellis, Nabeel A Affara
The male-specific region of the Y chromosome is evolutionarily predisposed to accumulate genes important for spermatogenesis. Recent work in this laboratory identified two novel Y-linked transcripts that were upregulated in the testis in response to deletions on the chromosome arm Yq. This article reports the further characterisation of these two transcripts and their comparison to related X and autosomal genes. Both map to chromosome arm Yp, outside the Sxr ( b ) deletion interval, both are present in at least two copies on the Y, and both are expressed specifically in spermatids...
April 2009: Mammalian Genome: Official Journal of the International Mammalian Genome Society
Rodrigo González-Romero, Josefina Méndez, Juan Ausió, José M Eirín-López
Histone H2A.Bbd (Barr body-deficient) is a novel histone variant which is largely excluded from the inactive X chromosome of mammals. Discovered only 6 years ago, H2A.Bbd displays very unusual structural and functional properties, for instance, it is relatively shorter and only 48% identical compared to H2A, lacking both the typical C-terminal tail of the H2A family and the very last sequence of the docking domain, making it the most specialized among all histone variants known to date. Indeed, molecular evolutionary analyses have shown that H2A...
April 30, 2008: Gene
Jiansheng Zhou, Jun Y Fan, Danny Rangasamy, David J Tremethick
Although it is believed that the interconversion between permissive and refractory chromatin structures is important in regulating gene transcription, this process is poorly understood. Central to addressing this issue is to elucidate how a nucleosomal array folds into higher-order chromatin structures. Such findings can then provide new insights into how the folding process is regulated to yield different functional states. Using well-defined in vitro chromatin-assembly and transcription systems, we show that a small acidic region on the surface of the nucleosome is crucial both for the folding of a nucleosomal template into the 30-nm chromatin fiber and for the efficient repression of transcription, thereby providing a mechanistic link between these two essential processes...
November 2007: Nature Structural & Molecular Biology
José María Eirín-López, Toyotaka Ishibashi, Juan Ausió
Molecular evolutionary analyses revealed that histone H2A.Bbd is a highly variable quickly evolving mammalian replacement histone variant, in striking contrast to all other histones. At the nucleotide level, this variability appears to be the result of a larger amount of nonsynonymous variation, which affects to a lesser extent, the structural domain of the protein comprising the histone fold. The resulting amino acid sequence diversity can be predicted to affect the internucleosomal and intranucleosomal histone interactions...
January 2008: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Hervé Menoni, Didier Gasparutto, Ali Hamiche, Jean Cadet, Stefan Dimitrov, Philippe Bouvet, Dimitar Angelov
In eukaryotes, base excision repair (BER) is responsible for the repair of oxidatively generated lesions. The mechanism of BER on naked DNA substrates has been studied in detail, but how it operates on chromatin remains unclear. Here we have studied the mechanism of BER by introducing a single 8-oxo-7,8-dihydroguanine (8-oxoG) lesion in the DNA of reconstituted positioned conventional and histone variant H2A.Bbd nucleosomes. We found that 8-oxoguanine DNA glycosylase, apurinic/apyrimidinic endonuclease, and polymerase beta activities were strongly reduced in both types of nucleosomes...
September 2007: Molecular and Cellular Biology
Fabien Montel, Emeline Fontaine, Philippe St-Jean, Martin Castelnovo, Cendrine Faivre-Moskalenko
We propose a combined experimental (atomic force microscopy) and theoretical study of the structural and dynamical properties of nucleosomes. In contrast to biochemical approaches, this method allows us to determine simultaneously the DNA-complexed length distribution and nucleosome position in various contexts. First, we show that differences in the nucleoproteic structure observed between conventional H2A and H2A.Bbd variant nucleosomes induce quantitative changes in the length distribution of DNA-complexed with histones...
July 15, 2007: Biophysical Journal
Cécile-Marie Doyen, Fabien Montel, Thierry Gautier, Hervé Menoni, Cyril Claudet, Marlène Delacour-Larose, Dimitri Angelov, Ali Hamiche, Jan Bednar, Cendrine Faivre-Moskalenko, Philippe Bouvet, Stefan Dimitrov
The histone variant H2A.Bbd appeared to be associated with active chromatin, but how it functions is unknown. We have dissected the properties of nucleosome containing H2A.Bbd. Atomic force microscopy (AFM) and electron cryo-microscopy (cryo-EM) showed that the H2A.Bbd histone octamer organizes only approximately 130 bp of DNA, suggesting that 10 bp of each end of nucleosomal DNA are released from the octamer. In agreement with this, the entry/exit angle of the nucleosomal DNA ends formed an angle close to 180 degrees and the physico-chemical analysis pointed to a lower stability of the variant particle...
September 20, 2006: EMBO Journal
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