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https://www.readbyqxmd.com/read/28985346/single-molecule-kinetic-analysis-of-hp1-chromatin-binding-reveals-a-dynamic-network-of-histone-modification-and-dna-interactions
#1
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...
August 3, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28977666/chd3-and-chd4-form-distinct-nurd-complexes-with-different-yet-overlapping-functionality
#2
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...
August 28, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28963472/zfp296-negatively-regulates-h3k9-methylation-in-embryonic-development-as-a-component-of-heterochromatin
#3
Takumi Matsuura, Satsuki Miyazaki, Tatsushi Miyazaki, Fumi Tashiro, Jun-Ichi Miyazaki
The Cys2/His2-type zinc finger protein Zfp296 has been implicated in stem cell pluripotency and tumor pathogenesis. However, its mechanisms remain elusive. Here, we demonstrated that a Zfp296 deficiency in mice impairs germ-cell development and embryonic growth. Zfp296 was intracellularly localized to heterochromatin in embryos. A GST-Zfp296 pull-down experiment using ES cell nuclear extract followed by LC-MS/MS showed that Zfp296 interacts with component proteins of heterochromatin (such as HP1, Dnmt1, Dnmt3b, and ATRX) and the NuRD complex...
September 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28960920/a-proteo-genomic-analysis-of-haptoglobin-in-malaria
#4
Gauri Awasthi, Suchi Tyagi, Vipin Kumar, Sandip Kumar Patel, Dharmendar Rojh, Vijeth Sakrappanavar, Sanjay Kumar Kochar, Arunansu Talukdar, Biaus Samanta, Aparup Das, Sanjeeva Srivastava, Swati Patankar
Haptoglobin (Hp), an acute phase inflammatory protein has been associated with malaria pathogenesis in several proteomics studies. The gene has two co-dominant alleles: Hp1 and Hp2 that produce three genotypes: Hp1/Hp1, Hp1/Hp2 and Hp2/Hp2. In this study, we perform validation of the proteomics data with Multiple Reaction Monitoring Mass Spectroscopy (MRM-MS). We further analyze the association of the Hp gene variants with severe, non-severe malaria and community (healthy) controls using genotyping PCRs and DNA sequencing...
September 27, 2017: Proteomics. Clinical Applications
https://www.readbyqxmd.com/read/28942425/chromosome-healing-is-promoted-by-the-telomere-cap-component-hiphop-in-drosophila
#5
Rebeccah L Kurzhals, Laura Fanti, A C Gonzalez Ebsen, Yikang S Rong, Sergio Pimpinelli, Kent G Golic
The addition of a new telomere onto a chromosome break, a process termed healing, has been studied extensively in organisms that utilize telomerase to maintain their telomeres. In comparison, relatively little is known about how new telomeres are constructed on broken chromosomes in organisms that do not use telomerase. Chromosome healing was studied in somatic and germline cells of Drosophila melanogaster, a non-telomerase species. We observed, for the first time, that broken chromosomes can be healed in somatic cells...
September 23, 2017: Genetics
https://www.readbyqxmd.com/read/28942089/biochemical-basis-for-distinct-roles-of-the-heterochromatin-proteins-swi6-and-chp2
#6
R Stefan Isaac, Serena Sanulli, Ryan Tibble, Michael Hornsby, Matthew Ravalin, Charles S Craik, John D Gross, Geeta J Narlikar
Heterochromatin protein 1 (HP1) family proteins are conserved chromatin binding proteins involved in gene silencing, chromosome packaging, and chromosome segregation. These proteins recognize histone H3 lysine 9 methylated tails via their chromodomain (CD) and recruit additional ligand proteins with diverse activities through their dimerization domain, the chromoshadow domain (CSD). Species that have HP1 proteins possess multiple paralogs that perform non-overlapping roles in vivo. How different HP1 proteins, which are highly conserved, perform different functions is not well understood...
September 20, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28916764/rapid-and-reversible-epigenome-editing-by-endogenous-chromatin-regulators
#7
Simon M G Braun, Jacob G Kirkland, Emma J Chory, Dylan Husmann, Joseph P Calarco, Gerald R Crabtree
Understanding the causal link between epigenetic marks and gene regulation remains a central question in chromatin biology. To edit the epigenome we developed the FIRE-Cas9 system for rapid and reversible recruitment of endogenous chromatin regulators to specific genomic loci. We enhanced the dCas9-MS2 anchor for genome targeting with Fkbp/Frb dimerizing fusion proteins to allow chemical-induced proximity of a desired chromatin regulator. We find that mSWI/SNF (BAF) complex recruitment is sufficient to oppose Polycomb within minutes, leading to activation of bivalent gene transcription in mouse embryonic stem cells...
September 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/28900795/haptoglobin-levels-but-not-hp1-hp2-polymorphism-are-associated-with-polycystic-ovary-syndrome
#8
Laura M L Carvalho, Cláudia N Ferreira, Daisy K D de Oliveira, Kathryna F Rodrigues, Rita C F Duarte, Márcia F A Teixeira, Luana B Xavier, Ana Lúcia Candido, Fernando M Reis, Ieda F O Silva, Fernanda M F Campos, Karina B Gomes
PURPOSE: Proteomic studies suggest an association between haptoglobin (Hp) and polycystic ovary syndrome (PCOS). Hp is a classic inflammatory marker and binds to the intravascular hemoglobin, avoiding the oxidative damages that can be caused by free hemoglobin. Inflammation and oxidative stress are important in the pathogenesis of the PCOS, one of the most frequent metabolic diseases in women. METHODS: To validate these proteomic studies, we developed a controlled cross-sectional study that aimed to evaluate the Hp levels and allelic and genotypic frequencies of Hp1-Hp2 polymorphism in Brazilian women with PCOS...
September 13, 2017: Journal of Assisted Reproduction and Genetics
https://www.readbyqxmd.com/read/28886332/evolving-models-of-heterochromatin-from-foci-to-liquid-droplets
#9
Antonis Tatarakis, Reza Behrouzi, Danesh Moazed
Two recent papers (Larson et al., 2017; Strom et al., 2017) in Nature propose that heterochromatic domains are organized into phase-separated liquid compartments. Here we highlight the main findings that support the liquid-like nature of HP1 domains and discuss their functional implications in gene silencing and genome organization.
September 7, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28881656/brd4-facilitates-dna-damage-response-and-represses-cbx5-heterochromatin-protein-1-hp1
#10
Georgios Pongas, Marianne K Kim, Dong J Min, Carrie D House, Elizabeth Jordan, Natasha Caplen, Sirisha Chakka, Joyce Ohiri, Michael J Kruhlak, Christina M Annunziata
Ovarian cancer (OC) is a heterogeneous disease characterized by defective DNA repair. Very few targets are universally expressed in the high grade serous (HGS) subtype. We previously identified that CHK1 was overexpressed in most of HGSOC. Here, we sought to understand the DNA damage response (DDR) to CHK1 inhibition and increase the anti-tumor activity of this pathway. We found BRD4 suppression either by siRNA or BRD4 inhibitor JQ1 enhanced the cytotoxicity of CHK1 inhibition. Interestingly, BRD4 was amplified and/or upregulated in a subset of HGSOC with statistical correlation to overall survival...
August 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28855512/atrx-is-a-regulator-of-therapy-induced-senescence-in-human-cells
#11
Marta Kovatcheva, Will Liao, Mary E Klein, Nicolas Robine, Heather Geiger, Aimee M Crago, Mark A Dickson, William D Tap, Samuel Singer, Andrew Koff
Senescence is a state of stable cell cycle exit with important implications for development and disease. Here, we demonstrate that the chromatin remodeling enzyme ATRX is required for therapy-induced senescence. ATRX accumulates in nuclear foci and is required for therapy-induced senescence in multiple types of transformed cells exposed to either DNA damaging agents or CDK4 inhibitors. Mobilization into foci depends on the ability of ATRX to interact with H3K9me3 histone and HP1. Foci form soon after cells exit the cell cycle, before other hallmarks of senescence appear...
August 30, 2017: Nature Communications
https://www.readbyqxmd.com/read/28813671/oct4-and-sox2-work-as-transcriptional-activators-in-reprogramming-human-fibroblasts
#12
Santosh Narayan, Gene Bryant, Shivangi Shah, Georgina Berrozpe, Mark Ptashne
SOX2 and OCT4, in conjunction with KLF4 and cMYC, are sufficient to reprogram human fibroblasts to induced pluripotent stem cells (iPSCs), but it is unclear if they function as transcriptional activators or as repressors. We now show that, like OCT4, SOX2 functions as a transcriptional activator. We substituted SOX2-VP16 (a strong activator) for wild-type (WT) SOX2, and we saw an increase in the efficiency and rate of reprogramming, whereas the SOX2-HP1 fusion (a strong repressor) eliminated reprogramming...
August 15, 2017: Cell Reports
https://www.readbyqxmd.com/read/28810153/evaluation-of-affibody-molecule-based-pna-mediated-radionuclide-pretargeting-development-of-an-optimized-conjugation-protocol-and-177-lu-labeling
#13
Mohamed Altai, Kristina Westerlund, Justin Velletta, Bogdan Mitran, Hadis Honarvar, Amelie Eriksson Karlström
INTRODUCTION: We have previously developed a pretargeting approach for affibody-mediated cancer therapy based on PNA-PNA hybridization. In this article we have further developed this approach by optimizing the production of the primary agent, ZHER2:342-SR-HP1, and labeling the secondary agent, HP2, with the therapeutic radionuclide (177)Lu. We also studied the biodistribution profile of (177)Lu-HP2 in mice, and evaluated pretargeting with (177)Lu-HP2 in vitro and in vivo. METHODS: The biodistribution profile of (177)Lu-HP2 was evaluated in NMRI mice and compared to the previously studied (111)In-HP2...
July 12, 2017: Nuclear Medicine and Biology
https://www.readbyqxmd.com/read/28782354/ternary-electrochemiluminescence-system-based-on-rubrene-microrods-as-luminophore-and-pt-nanomaterials-as-coreaction-accelerator-for-ultrasensitive-detection-of-microrna-from-cancer-cells
#14
Jia-Li Liu, Zhi-Ling Tang, Ying Zhuo, Ya-Qin Chai, Ruo Yuan
As the only endogenous coreactant in the electrochemiluminescence (ECL) system, the dissolved O2 was the ideal candidate due to the mild reaction and easy operation, but compared to S2O8(2-), the dissolved O2 with weaker redox activity suffers from the poor enhancement effect of the luminophore, which restricted the further application in bioanalysis. Here, a high-intense ECL signal was gained by the employing of Pt nanomaterials as a coreaction accelerator to generate more of the intermediate of dissolved O2 to promote the coreaction efficiency...
September 5, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28698785/haptoglobin-phenotypes-and-susceptibility-to-schistosoma-parasites-infection-in-central-sudan
#15
Ashraf Siddig Yousif, Atif Abdelrahman Elagib
Haptoglobin (Hp) is an acute phase protein that binds the free hemoglobin (Hb), thus preventing iron loss and renal damage. Hp also has antioxidative and immunomodulatory properties. Three Hp phenotypes have been identified in human: Hp1-1, Hp2-1, and Hp2-2. Hp polymorphisms have been related to susceptibility of various diseases. In this study, we aimed to assess the possible association of Hp phenotypes polymorphism to Schistosoma parasites infection in central Sudan. We have investigated the Hp phenotypes polymorphism distribution in the serum of 125 (93 S...
2017: Mediterranean Journal of Hematology and Infectious Diseases
https://www.readbyqxmd.com/read/28692189/diversification-of-hp1-like-chromo-domain-proteins-in-tetrahymena-thermophila
#16
Emily A Wiley, Scott Horrell, Alyssa Yoshino, Cara C Schornak, Claire Bagnani, Douglas L Chalker
Proteins that possess a chromo domain are well-known for their roles in heterochromatin assembly and maintenance. The Heterochromatin Protein 1 (HP1) family, with a chromo domain and carboxy-terminal chromo shadow domain, targets heterochromatin through interaction with histone H3 methylated on lysine 9 (H3K9me2/3). The structural and functional diversity of these proteins observed in both fission yeast and metazoans correlate with chromatin specialization. To expand these studies, we examined chromo domain proteins in the ciliate Tetrahymena thermophila, which has functionally diverse and developmentally regulated heterochromatin domains...
July 10, 2017: Journal of Eukaryotic Microbiology
https://www.readbyqxmd.com/read/28684548/lem-domain-proteins-are-lost-during-human-spermiogenesis-but-baf-and-baf-l-persist
#17
Razan A Elkhatib, Marine Paci, Romain Boissier, Guy Longepied, Yasmina Auguste, Vincent Achard, Patrice Bourgeois, Nicolas Levy, Nicolas Branger, Michael J Mitchell, Catherine Metzler-Guillemain
During spermiogenesis the spermatid nucleus is elongated, and dramatically reduced in size with protamines replacing histones to produce a highly compacted chromatin. After fertilisation, this process is reversed in the oocyte to form the male pronucleus. Emerging evidence, including the coordinated loss of the nuclear lamina (NL) and the histones, supports the involvement of the NL in spermatid nuclear remodelling, but how the NL links to the chromatin is not known. In somatic cells, interactions between the NL and the chromatin have been demonstrated: LEM-domain proteins and LBR interact with the NL and, respectively, the chromatin proteins BAF and HP1...
July 6, 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/28659611/a-common-deletion-in-the-haptoglobin-gene-associated-with-blood-cholesterol-levels-among-chinese-women
#18
Neil S Zheng, Lisa A Bastarache, Julie A Bastarache, Yingchang Lu, Lorraine B Ware, Xiao-Ou Shu, Joshua C Denny, Jirong Long
Haptoglobin (HP) protein plays a critical role in binding and removing free hemoglobin from blood. A deletion in the HP gene affects the protein structure and function. A recent study developed a novel method to impute this variant and discovered significant association of this variant with low-density lipoprotein (LDL) and total cholesterol levels among European descendants. In the present study, we investigated this variant among 3608 Chinese women. Consistent with findings from Europeans, we found significant associations between the deletion with lower cholesterol levels; women homozygous for the deletion allele (HP1-HP1), had a lower level of total cholesterol (-4...
October 2017: Journal of Human Genetics
https://www.readbyqxmd.com/read/28636604/liquid-droplet-formation-by-hp1%C3%AE-suggests-a-role-for-phase-separation-in-heterochromatin
#19
Adam G Larson, Daniel Elnatan, Madeline M Keenen, Michael J Trnka, Jonathan B Johnston, Alma L Burlingame, David A Agard, Sy Redding, Geeta J Narlikar
Gene silencing by heterochromatin is proposed to occur in part as a result of the ability of heterochromatin protein 1 (HP1) proteins to spread across large regions of the genome, compact the underlying chromatin and recruit diverse ligands. Here we identify a new property of the human HP1α protein: the ability to form phase-separated droplets. While unmodified HP1α is soluble, either phosphorylation of its N-terminal extension or DNA binding promotes the formation of phase-separated droplets. Phosphorylation-driven phase separation can be promoted or reversed by specific HP1α ligands...
July 13, 2017: Nature
https://www.readbyqxmd.com/read/28636597/phase-separation-drives-heterochromatin-domain-formation
#20
Amy R Strom, Alexander V Emelyanov, Mustafa Mir, Dmitry V Fyodorov, Xavier Darzacq, Gary H Karpen
Constitutive heterochromatin is an important component of eukaryotic genomes that has essential roles in nuclear architecture, DNA repair and genome stability, and silencing of transposon and gene expression. Heterochromatin is highly enriched for repetitive sequences, and is defined epigenetically by methylation of histone H3 at lysine 9 and recruitment of its binding partner heterochromatin protein 1 (HP1). A prevalent view of heterochromatic silencing is that these and associated factors lead to chromatin compaction, resulting in steric exclusion of regulatory proteins such as RNA polymerase from the underlying DNA...
July 13, 2017: Nature
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