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HP1 proteins

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https://www.readbyqxmd.com/read/28916764/rapid-and-reversible-epigenome-editing-by-endogenous-chromatin-regulators
#1
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
#2
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/28881656/brd4-facilitates-dna-damage-response-and-represses-cbx5-heterochromatin-protein-1-hp1
#3
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/28698785/haptoglobin-phenotypes-and-susceptibility-to-schistosoma-parasites-infection-in-central-sudan
#4
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
#5
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
#6
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
#7
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...
June 29, 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
#8
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
#9
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
https://www.readbyqxmd.com/read/28548929/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...
May 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28514126/-haptoglobin-polymorphism-as-an-independent-predictor-of-diabetic-nephropathy-and-retinopathy
#11
Inbal Dahan, Nadia Thauho, Farid Nakhoul, Nakhoul Nakhoul, Hanin Jabaly, Evgeny Farber
The antioxidant protein haptoglobin (Hp) plays a major role in the development of diabetic complications such as diabetic nephropathy and retinopathy. In humans, two alleles of Hp were identified: 1 and 2 with three possible genotypes: 1-1, 2-1, and 2-2. The Hp protein products differ in their biochemical and biophysical properties, such as their antioxidant capacity. The Hp1 protein is superior to the Hp2 protein in binding to free hemoglobin and neutralizing its oxidative potential and the accompanying renal and retinal injury...
July 2016: Harefuah
https://www.readbyqxmd.com/read/28487337/haptoglobin-hp2-variant-promotes-premature-cardiovascular-death-in-stroke-survivors
#12
Petra Ijäs, Susanna Melkas, Jani Saksi, Antti Jula, Matti Jauhiainen, Niku Oksala, Tarja Pohjasvaara, Markku Kaste, Pekka J Karhunen, Perttu Lindsberg, Timo Erkinjuntti
BACKGROUND AND PURPOSE: Haptoglobin (Hp) is an acute phase plasma protein protecting tissues from oxidative damage. It exists in 2 variant alleles (hp1/hp2) giving rise to 3 protein isoforms with different biochemical properties and efficiency to limit oxidative stress. We previously found that hp2 variant is associated with stroke risk in the patients with carotid stenosis and the risk of ischemic cardiovascular events in a general population cohort. This study examined the hypothesis that Hp genotype is associated with general cardiovascular risk in patients with stroke...
June 2017: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/28483815/drosophila-dalmatian-combines-sororin-and-shugoshin-roles-in-establishment-and-protection-of-cohesion
#13
Takashi Yamada, Eri Tahara, Mai Kanke, Keiko Kuwata, Tomoko Nishiyama
Sister chromatid cohesion is crucial to ensure chromosome bi-orientation and equal chromosome segregation. Cohesin removal via mitotic kinases and Wapl has to be prevented in pericentromeric regions in order to protect cohesion until metaphase, but the mechanisms of mitotic cohesion protection remain elusive in Drosophila Here, we show that dalmatian (Dmt), an ortholog of the vertebrate cohesin-associated protein sororin, is required for protection of mitotic cohesion in flies. Dmt is essential for cohesion establishment during interphase and is enriched on pericentromeric heterochromatin...
June 1, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28392109/compartmentalization-of-dna-damage-response-between-heterochromatin-and-euchromatin-is-mediated-by-distinct-h2a-histone-variants
#14
Zdravko J Lorković, Chulmin Park, Malgorzata Goiser, Danhua Jiang, Marie-Therese Kurzbauer, Peter Schlögelhofer, Frédéric Berger
DNA double-strand break (DSB) repair depends on the ataxia telangiectasia mutated (ATM) kinase that phosphorylates the conserved C-terminal SQ motif present in the histone variant H2A.X [1-7]. In constitutive heterochromatin of mammals, DSB repair is delayed and relies on phosphorylation of the proteins HP1 and KAP1 by ATM [2, 8-14]. However, KAP1 is not conserved in plants and the HP1-related protein Like-HP1 (LHP1) is not localized at constitutive heterochromatin [15], suggesting that in plants, alternative mechanisms could be responsible for repair of DSBs in heterochromatin...
April 24, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28385889/substituted-cysteine-accessibility-method-scam-analysis-of-the-transport-domain-of-human-concentrative-nucleoside-transporter-3-hcnt3-and-other-family-members-reveals-features-of-structural-and-functional-importance
#15
Ras Mulinta, Sylvia Y M Yao, Amy M L Ng, Carol E Cass, James D Young
The human SLC28 family of concentrative nucleoside transporter (CNT) proteins has three members: hCNT1, hCNT2, and hCNT3. Na(+)-coupled hCNT1 and hCNT2 transport pyrimidine and purine nucleosides, respectively, whereas hCNT3 transports both pyrimidine and purine nucleosides utilizing Na(+) and/or H(+) electrochemical gradients. Escherichia coli CNT family member NupC resembles hCNT1 in permeant selectivity but is H(+)-coupled. Using heterologous expression in Xenopus oocytes and the engineered cysteine-less hCNT3 protein hCNT3(C-), substituted cysteine accessibility method analysis with the membrane-impermeant thiol reactive reagent p-chloromercuribenzene sulfonate was performed on the transport domain (interfacial helix 2, hairpin 1, putative transmembrane domain (TM) 7, and TM8), as well as TM9 of the scaffold domain of the protein...
June 9, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28369503/populus-simonii-%C3%A3-populus-nigra-wrky70-is-involved-in-salt-stress-and-leaf-blight-disease-responses
#16
Hui Zhao, Jing Jiang, Kailong Li, Guifeng Liu
WRKY transcription factors (TFs) are important regulators in the complex stress response signaling networks in plants, but the detailed mechanisms underlying these regulatory networks have not been fully characterized. In the present study, we identified a Group III WRKY gene (PsnWRKY70, Potri.016G137900) from Populussimonii × Populusnigra and explored its function under salt and pathogen stresses. The promoter sequence that is located 2471-bp upstream from the start codon (SC) of PsnWRKY70 contained many stress-responsive cis-elements...
June 1, 2017: Tree Physiology
https://www.readbyqxmd.com/read/28346356/microinjection-of-antibodies-targeting-the-lamin-a-c-histone-binding-site-blocks-mitotic-entry-and-reveals-separate-chromatin-interactions-with-hp1-cenpb-and-pml
#17
Charles R Dixon, Melpomeni Platani, Alexandr A Makarov, Eric C Schirmer
Lamins form a scaffold lining the nucleus that binds chromatin and contributes to spatial genome organization; however, due to the many other functions of lamins, studies knocking out or altering the lamin polymer cannot clearly distinguish between direct and indirect effects. To overcome this obstacle, we specifically targeted the mapped histone-binding site of A/C lamins by microinjecting antibodies specific to this region predicting that this would make the genome more mobile. No increase in chromatin mobility was observed; however, interestingly, injected cells failed to go through mitosis, while control antibody-injected cells did...
March 25, 2017: Cells
https://www.readbyqxmd.com/read/28294943/a-team-of-heterochromatin-factors-collaborates-with-small-rna-pathways-to-combat-repetitive-elements-and-germline-stress
#18
Alicia N McMurchy, Przemyslaw Stempor, Tessa Gaarenstroom, Brian Wysolmerski, Yan Dong, Darya Aussianikava, Alex Appert, Ni Huang, Paulina Kolasinska-Zwierz, Alexandra Sapetschnig, Eric A Miska, Julie Ahringer
Repetitive sequences derived from transposons make up a large fraction of eukaryotic genomes and must be silenced to protect genome integrity. Repetitive elements are often found in heterochromatin; however, the roles and interactions of heterochromatin proteins in repeat regulation are poorly understood. Here we show that a diverse set of C. elegans heterochromatin proteins act together with the piRNA and nuclear RNAi pathways to silence repetitive elements and prevent genotoxic stress in the germ line. Mutants in genes encoding HPL-2/HP1, LIN-13, LIN-61, LET-418/Mi-2, and H3K9me2 histone methyltransferase MET-2/SETDB1 also show functionally redundant sterility, increased germline apoptosis, DNA repair defects, and interactions with small RNA pathways...
March 15, 2017: ELife
https://www.readbyqxmd.com/read/28293301/histone-peptide-microarray-screen-of-chromo-and-tudor-domains-defines-new-histone-lysine-methylation-interactions
#19
Erin K Shanle, Stephen A Shinsky, Joseph B Bridgers, Narkhyun Bae, Cari Sagum, Krzysztof Krajewski, Scott B Rothbart, Mark T Bedford, Brian D Strahl
BACKGROUND: Histone posttranslational modifications (PTMs) function to regulate chromatin structure and function in part through the recruitment of effector proteins that harbor specialized "reader" domains. Despite efforts to elucidate reader domain-PTM interactions, the influence of neighboring PTMs and the target specificity of many reader domains is still unclear. The aim of this study was to use a high-throughput histone peptide microarray platform to interrogate 83 known and putative histone reader domains from the chromo and Tudor domain families to identify their interactions and characterize the influence of neighboring PTMs on these interactions...
2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/28293300/silencing-markers-are-retained-on-pericentric-heterochromatin-during-murine-primordial-germ-cell-development
#20
Aristea Magaraki, Godfried van der Heijden, Esther Sleddens-Linkels, Leonidas Magarakis, Wiggert A van Cappellen, Antoine H F M Peters, Joost Gribnau, Willy M Baarends, Maureen Eijpe
BACKGROUND: In the nuclei of most mammalian cells, pericentric heterochromatin is characterized by DNA methylation, histone modifications such as H3K9me3 and H4K20me3, and specific binding proteins like heterochromatin-binding protein 1 isoforms (HP1 isoforms). Maintenance of this specialized chromatin structure is of great importance for genome integrity and for the controlled repression of the repetitive elements within the pericentric DNA sequence. Here we have studied histone modifications at pericentric heterochromatin during primordial germ cell (PGC) development using different fixation conditions and fluorescent immunohistochemical and immunocytochemical protocols...
2017: Epigenetics & Chromatin
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