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HP1 proteins

Christian A Schaer, Catherine Owczarek, Jeremy W Deuel, Stefan Schauer, Jin Hyen Baek, Ayla Yalamanoglu, Matthew P Hardy, Pierre D Scotney, Peter M Schmidt, Matthias Pelzing, Peter Soupourmas, Paul W Buehler, Dominik J Schaer
BACKGROUND: Preclinical studies have evaluated haptoglobin (Hp) polymers from pooled human plasma as a therapeutic protein to attenuate toxic effects of cell-free hemoglobin (Hb). Proof of concept studies have demonstrated efficacy of Hp in hemolysis associated with transfusion and sickle cell anemia. However, phenotype-specific Hp products might be desirable to exploit phenotype specific activities of Hp 1-1 versus Hp 2-2, offering opportunities for recombinant therapeutics. Prohaptoglobin (proHp) is the primary translation product of the Hp mRNA...
March 15, 2018: BMC Biotechnology
Seema Rani, Ravinder Kumar, Prasad Kumarasinghe, Supriya Bhardwaj, Niharika Srivastava, Aaisha Madaan, Davinder Parsad
BACKGROUND: Idiopathic guttate hypomelanosis (IGH) is a pigmentary disorder of unknown pathogenesis characterized by small discrete white macules. In the skin, epidermal melanin unit between melanocytes and keratinocytes is responsible for melanin synthesis and equal distribution of melanin pigment. OBJECTIVE: Therefore, this study was designed to check the role of melanocytes in the pathogenesis of IGH. METHODS: For this study, six IGH patients and six controls were enrolled...
March 8, 2018: International Journal of Dermatology
Sabine A Fraschka, Michael Filarsky, Regina Hoo, Igor Niederwieser, Xue Yan Yam, Nicolas M B Brancucci, Franziska Mohring, Annals T Mushunje, Ximei Huang, Peter R Christensen, Francois Nosten, Zbynek Bozdech, Bruce Russell, Robert W Moon, Matthias Marti, Peter R Preiser, Richárd Bártfai, Till S Voss
Heterochromatin-dependent gene silencing is central to the adaptation and survival of Plasmodium falciparum malaria parasites, allowing clonally variant gene expression during blood infection in humans. By assessing genome-wide heterochromatin protein 1 (HP1) occupancy, we present a comprehensive analysis of heterochromatin landscapes across different Plasmodium species, strains, and life cycle stages. Common targets of epigenetic silencing include fast-evolving multi-gene families encoding surface antigens and a small set of conserved HP1-associated genes with regulatory potential...
February 22, 2018: Cell Host & Microbe
Qi Yi, Qinfu Chen, Cai Liang, Haiyan Yan, Zhenlei Zhang, Xingfeng Xiang, Miao Zhang, Feifei Qi, Linli Zhou, Fangwei Wang
Heterochromatin protein-1 (HP1) is a key component of heterochromatin. Reminiscent of the cohesin complex which mediates sister-chromatid cohesion, most HP1 proteins in mammalian cells are displaced from chromosome arms during mitotic entry, whereas a pool remains at the heterochromatic centromere region. The function of HP1 at mitotic centromeres remains largely elusive. Here, we show that double knockout (DKO) of HP1α and HP1γ causes defective mitosis progression and weakened centromeric cohesion. While mutating the chromoshadow domain (CSD) prevents HP1α from protecting sister-chromatid cohesion, centromeric targeting of HP1α CSD alone is sufficient to rescue the cohesion defects in HP1 DKO cells...
February 28, 2018: EMBO Reports
Jan G Ruppert, Kumiko Samejima, Melpomeni Platani, Oscar Molina, Hiroshi Kimura, A Arockia Jeyaprakash, Shinya Ohta, William C Earnshaw
The chromosomal passenger complex (CPC) is directed to centromeres during mitosis via binding to H3T3ph and Sgo1. Whether and how heterochromatin protein 1α (HP1α) influences CPC localisation and function during mitotic entry is less clear. Here, we alter HP1α dynamics by fusing it to a CENP-B DNA-binding domain. Tethered HP1 strongly recruits the CPC, destabilising kinetochore-microtubule interactions and activating the spindle assembly checkpoint. During mitotic exit, the tethered HP1 traps active CPC at centromeres...
February 21, 2018: EMBO Journal
Natalia Akulenko, Sergei Ryazansky, Valeriya Morgunova, Pavel A Komarov, Ivan Olovnikov, Chantal Vaury, Silke Jensen, Alla Kalmykova
Expression of transposable elements in the germline is controlled by Piwi-interacting (pi) RNAs produced by genomic loci termed piRNA clusters and associated with Rhino, a Heterochromatin Protein 1 (HP1) homolog. Previously, we have shown that transgenes containing a fragment of the I retrotransposon form de novo piRNA clusters in the Drosophila germline providing suppression of I-element activity. We noted that identical transgenes located in different genomic sites vary considerably in piRNA production and classified them as "strong" and "weak" piRNA clusters...
January 22, 2018: RNA
Nur Zafirah Zaidan, Kolin J Walker, Jaime E Brown, Leah V Schaffer, Mark Scalf, Michael R Shortreed, Gopal Iyer, Lloyd M Smith, Rupa Sridharan
The heterochromatin protein 1 (HP1) family is involved in various functions with maintenance of chromatin structure. During murine somatic cell reprogramming, we find that early depletion of HP1γ reduces the generation of induced pluripotent stem cells, while late depletion enhances the process, with a concomitant change from a centromeric to nucleoplasmic localization and elongation-associated histone H3.3 enrichment. Depletion of heterochromatin anchoring protein SENP7 increased reprogramming efficiency to a similar extent as HP1γ, indicating the importance of HP1γ release from chromatin for pluripotency acquisition...
January 17, 2018: Stem Cell Reports
Shufeng Liu, Yishen Tian, Shanshan Zhang, Li Wang
A new modular nanoswitch was described for versatile, rapid (within 1 h), homogeneous and sensitive protein detection. The system employs two hairpins (HP1 and HP2) that can be reciprocally recognized through the apical loop-loop interaction. The HP2 possesses a conformation-switching stem-loop structure with the appended single-stranded tails on each end, which can hybridize with the recognition element-conjugated DNA strands to construct a protein-responsive HP2 scaffold. It works according to a simple mix-and-detect assay format with the first formation of a kissing complex between HP1 and HP2 scaffold for fluorescence quenching and then the cascade propagation from the steric strain by protein binding to the dissociation of kissing complex for fluorescence recovery...
January 22, 2018: Chembiochem: a European Journal of Chemical Biology
Mingsha Zhao, Shanshan Zhang, Zhiqiang Chen, Changzhi Zhao, Li Wang, Shufeng Liu
Herein, an allosteric kissing complex-based electrochemical biosensor was ingeniously proposed for the simple, sensitive, regenerative and versatile detection of proteins. Two hairpins (Hp1 and Hp2) were designed and the Hp1 was immobilized on the electrode surface, which could form a kissing complex with Hp2 through the apical loop-loop or kissing interaction of the RNA-RNA base sequences. The Hp2 possesses the appended single-stranded tails on each end, which hybridize with the recognition element-conjugated DNA strands to construct a protein responsive switch of Hp2 scaffold...
January 9, 2018: Biosensors & Bioelectronics
Shinichi Machida, Yoshimasa Takizawa, Masakazu Ishimaru, Yukihiko Sugita, Satoshi Sekine, Jun-Ichi Nakayama, Matthias Wolf, Hitoshi Kurumizaka
Heterochromatin plays important roles in transcriptional silencing and genome maintenance by the formation of condensed chromatin structures, which determine the epigenetic status of eukaryotic cells. The trimethylation of histone H3 lysine 9 (H3K9me3), a target of heterochromatin protein 1 (HP1), is a hallmark of heterochromatin formation. However, the mechanism by which HP1 folds chromatin-containing H3K9me3 into a higher-order structure has not been elucidated. Here we report the three-dimensional structure of the H3K9me3-containing dinucleosomes complexed with human HP1α, HP1β, and HP1γ, determined by cryogenic electron microscopy with a Volta phase plate...
January 10, 2018: Molecular Cell
Ying Peng, Daxiu Li, Ruo Yuan, Yun Xiang
Abnormal concentrations of ATP are associated with many diseases and cancers, and quantitative detection of ATP is thus of great importance for disease diagnosis and prognosis. In the present work, we report a new dual recycling amplification sensor integrated with catalytic hairpin assembly (CHA) to achieve high sensitivity for fluorescent detection of ATP. The association of the target ATP with the aptamer beacons causes the allosteric structure switching of the aptamer beacons to expose the toehold regions, which hybridize with and unfold the fluorescently quenched hairpin signal probes (HP1) to recycle the target ATP and to trigger CHA between HP1 and the secondary hairpin probes (HP2) to form HP1/HP2 duplexes...
May 15, 2018: Biosensors & Bioelectronics
Laia Bosch-Presegué, Helena Raurell-Vila, Joshua K Thackray, Jessica González, Carmen Casal, Noriko Kane-Goldsmith, Miguel Vizoso, Jeremy P Brown, Antonio Gómez, Juan Ausió, Timo Zimmermann, Manel Esteller, Gunnar Schotta, Prim B Singh, Lourdes Serrano, Alejandro Vaquero
HP1 is a structural component of heterochromatin. Mammalian HP1 isoforms HP1α, HP1β, and HP1γ play different roles in genome stability, but their precise role in heterochromatin structure is unclear. Analysis of Hp1α(-/-), Hp1β(-/-), and Hp1γ(-/-) MEFs show that HP1 proteins have both redundant and unique functions within pericentric heterochromatin (PCH) and also act globally throughout the genome. HP1α confines H4K20me3 and H3K27me3 to regions within PCH, while its absence results in a global hyper-compaction of chromatin associated with a specific pattern of mitotic defects...
November 21, 2017: Cell Reports
Alexander I Shevchenko, Elena V Grigor'eva, Sergey P Medvedev, Irina S Zakharova, Elena V Dementyeva, Eugeny A Elisaphenko, Anastasia A Malakhova, Sophia V Pavlova, Suren M Zakian
In vole Microtus levis, cells of preimplantation embryo and extraembryonic tissues undergo imprinted X chromosome inactivation (iXCI) which is triggered by a long non-coding nuclear RNA, Xist. At early stages of iXCI, chromatin of vole inactive X chromosome is enriched with the HP1 heterochromatin-specific protein, trimethylated H3K9 and H4K20 attributable to constitutive heterochromatin. In the study, using vole trophoblast stem (TS) cells as a model of iXCI, we further investigated chromatin of the inactive X chromosome of M...
November 18, 2017: Chromosoma
Yiqin Ma, Laura Buttitta
BACKGROUND: Genome organization changes during development as cells differentiate. Chromatin motion becomes increasingly constrained and heterochromatin clusters as cells become restricted in their developmental potential. These changes coincide with slowing of the cell cycle, which can also influence chromatin organization and dynamics. Terminal differentiation is often coupled with permanent exit from the cell cycle, and existing data suggest a close relationship between a repressive chromatin structure and silencing of the cell cycle in postmitotic cells...
November 10, 2017: Epigenetics & Chromatin
Shih-Chieh Chang, Yi-Chun Lai, Yen-Chung Chen, Nai-Kuan Wang, Wei-Shu Wang, Jiun-I Lai
AIM: Lung cancer is typically categorized into small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). NSCLC comprises of the majority of lung cancer with a poor prognosis in advanced cases. Transcriptional profiling studies, including microarrays and RNA-sequencing studies, have significantly enriched our knowledge of gene expression patterns in NSCLC. A recent transcriptional profiling study identified high prevalence of CBX3/HP1-gamma upregulation in human NSCLC samples...
November 10, 2017: Asia-Pacific Journal of Clinical Oncology
Stefanie A Baril, Amber L Koenig, Mackenzie W Krone, Katherine I Albanese, Cyndi Qixin He, Ga Young Lee, Kendall N Houk, Marcey L Waters, Eric M Brustad
Trimethyllysine (Kme3) reader proteins are targets for inhibition due to their role in mediating gene expression. Although all such reader proteins bind Kme3 in an aromatic cage, the driving force for binding may differ; some readers exhibit evidence for cation-π interactions whereas others do not. We report a general unnatural amino acid mutagenesis approach to quantify the contribution of individual tyrosines to cation binding using the HP1 chromodomain as a model system. We demonstrate that two tyrosines (Y24 and Y48) bind to a Kme3-histone tail peptide via cation-π interactions, but linear free energy trends suggest they do not contribute equally to binding...
December 6, 2017: Journal of the American Chemical Society
Ben Gaastra, James Glazier, Diederik Bulters, Ian Galea
Haptoglobin (Hp) is a plasma protein involved in clearing extracellular haemoglobin and regulating inflammation; it exists as two genetic variants (Hp1 and Hp2). In a meta-analysis of six published studies, we confirm that Hp genotype affects short-term outcome (cerebral vasospasm and/or delayed cerebral ischemia) after subarachnoid haemorrhage (SAH) but not long-term outcome (Glasgow Outcome Score and modified Rankin Scale between one and three months). A closer examination of the heterozygous group revealed that the short-term outcome of Hp2-1 individuals clustered with that of Hp1-1 and not Hp2-2, suggesting that the presence of one Hp1 allele was sufficient to confer protection...
2017: Oxidative Medicine and Cellular Longevity
Jordan D Gessaman, Eric U Selker
Functionally different chromatin domains display distinct chemical marks. Constitutive heterochromatin is commonly associated with trimethylation of lysine 9 on histone H3 (H3K9me3), hypoacetylated histones, and DNA methylation, but the contributions of and interplay among these features are not fully understood. To dissect the establishment of heterochromatin, we investigated the relationships among these features using an in vivo tethering system in Neurospora crassa Artificial recruitment of the H3K9 methyltransferase DIM-5 (defective in methylation-5) induced H3K9me3 and DNA methylation at a normally active, euchromatic locus but did not bypass the requirement of DIM-7, previously implicated in the localization of DIM-5, indicating additional DIM-7 functionality...
November 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
Louise C Bryan, Daniel R Weilandt, Andreas L Bachmann, Sinan Kilic, Carolin C Lechner, Pascal D Odermatt, Georg E Fantner, Sandrine Georgeon, Oliver Hantschel, Vassily Hatzimanikatis, Beat Fierz
Chromatin recruitment of effector proteins involved in gene regulation depends on multivalent interaction with histone post-translational modifications (PTMs) and structural features of the chromatin fiber. Due to the complex interactions involved, it is currently not understood how effectors dynamically sample the chromatin landscape. Here, we dissect the dynamic chromatin interactions of a family of multivalent effectors, heterochromatin protein 1 (HP1) proteins, using single-molecule fluorescence imaging and computational modeling...
October 13, 2017: Nucleic Acids Research
Helen Hoffmeister, Andreas Fuchs, Fabian Erdel, Sophia Pinz, Regina Gröbner-Ferreira, Astrid Bruckmann, Rainer Deutzmann, Uwe Schwartz, Rodrigo Maldonado, Claudia Huber, Anne-Sarah Dendorfer, Karsten Rippe, Gernot Längst
CHD3 and CHD4 (Chromodomain Helicase DNA binding protein), two highly similar representatives of the Mi-2 subfamily of SF2 helicases, are coexpressed in many cell lines and tissues and have been reported to act as the motor subunit of the NuRD complex (nucleosome remodeling and deacetylase activities). Besides CHD proteins, NuRD contains several repressors like HDAC1/2, MTA2/3 and MBD2/3, arguing for a role as a transcriptional repressor. However, the subunit composition varies among cell- and tissue types and physiological conditions...
October 13, 2017: Nucleic Acids Research
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