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https://www.readbyqxmd.com/read/28218250/chromatin-remodeller-fun30-fft3-induces-nucleosome-disassembly-to-facilitate-rna-polymerase-ii-elongation
#1
Junwoo Lee, Eun Shik Choi, Hogyu David Seo, Keunsoo Kang, Joshua M Gilmore, Laurence Florens, Michael P Washburn, Joonho Choe, Jerry L Workman, Daeyoup Lee
Previous studies have revealed that nucleosomes impede elongation of RNA polymerase II (RNAPII). Recent observations suggest a role for ATP-dependent chromatin remodellers in modulating this process, but direct in vivo evidence for this is unknown. Here using fission yeast, we identify Fun30(Fft3) as a chromatin remodeller, which localizes at transcribing regions to promote RNAPII transcription. Fun30(Fft3) associates with RNAPII and collaborates with the histone chaperone, FACT, which facilitates RNAPII elongation through chromatin, to induce nucleosome disassembly at transcribing regions during RNAPII transcription...
February 20, 2017: Nature Communications
https://www.readbyqxmd.com/read/28215142/small-molecule-modulation-of-hdac6-activity-the-propitious-therapeutic-strategy-to-vanquish-neurodegenerative-disorders
#2
Shabir Ahmad Ganai
Histone deacetylases (HDACs) are epigenetic enzymes creating the transcriptionally inactive state of chromatin by erasing acetyl moiety from histone and non-histone substrates. HDAC6 modulates several biological pathways in dividing cells as well as in post-mitotic neurons, and has been implicated in the pathophysiology of neurodegeneration. The distinct cellular functions and survival in these cells are reliant on HDAC6-mediated processes including intracellular trafficking, chaperone-mediated stress responses, anti-oxidation and protein degradation...
February 8, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28213361/a-histone-chaperone-and-a-specific-transcription-factor-modulate-glabra2-expression-in-root-hair-development
#3
Jennifer Mach
No abstract text is available yet for this article.
February 17, 2017: Plant Cell
https://www.readbyqxmd.com/read/28186195/cenp-a-chromatin-disassembly-in-stressed-and-senescent-murine-cells
#4
Sabrine Hédouin, Giacomo Grillo, Ivana Ivkovic, Guillaume Velasco, Claire Francastel
Centromeres are chromosomal domains essential for genomic stability. We report here the remarkable transcriptional and epigenetic perturbations at murine centromeres in genotoxic stress conditions. A strong and selective transcriptional activation of centromeric repeats is detected within hours. This is followed by disorganization of centromeres with striking delocalization of nucleosomal CENP-A, the key determinant of centromere identity and function, in a mechanism requiring active transcription of centromeric repeats, the DNA Damage Response (DDR) effector ATM and chromatin remodelers/histone chaperones...
February 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28179136/expression-purification-and-characterization-of-the-human-mta2-rbbp7-complex
#5
Christoffer Brasen, Jerzy Dorosz, Anders Wiuf, Thomas Boesen, Osman Mirza, Michael Gajhede
The repressive Nucleosome Remodeling and histone Deacetylation (NuRD) complex remodels the chromatin structure by coupling ATP-dependent remodeling activity with histone deacetylase function and plays important roles in regulating gene transcription, DNA damage repair and chromatin assembly. The complex is composed of six subunits: Metastasis Associated proteins MTA1/2/3 initially recruit histone chaperones RBBP4/7 followed by the histone deacetylases HDAC1/2 forming a core complex. Further association of the CpG-binding protein MBD2/3, p66α/β and the ATP-dependent helicase CDH3/4 constitutes the NuRD complex...
February 4, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28146421/the-hdac-inhibitor-ar42-interacts-with-pazopanib-to-kill-trametinib-dabrafenib-resistant-melanoma-cells-in-vitro-and-in-vivo
#6
Laurence Booth, Jane L Roberts, Cindy Sander, John Lee, John M Kirkwood, Andrew Poklepovic, Paul Dent
Studies focused on the killing of activated B-RAF melanoma cells by the histone deacetylase (HDAC) inhibitor AR42. Compared to other tumor cell lines, PDX melanoma isolates were significantly more sensitive to AR42-induced killing. AR42 and the multi-kinase inhibitor pazopanib interacted to activate: an eIF2α-Beclin1 pathway causing autophagosome formation; an eIF2α-DR4/DR5/CD95 pathway; and an eIF2α-dependent reduction in the expression of c-FLIP-s, MCL-1 and BCL-XL. AR42 did not alter basal chaperone activity but increased the ability of pazopanib to inhibit HSP90, HSP70 and GRP78...
January 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28138144/chromatin-dynamics-during-the-cell-cycle-at-centromeres
#7
REVIEW
Sebastian Müller, Geneviève Almouzni
Centromeric chromatin undergoes major changes in composition and architecture during each cell cycle. These changes in specialized chromatin facilitate kinetochore formation in mitosis to ensure proper chromosome segregation. Thus, proper orchestration of centromeric chromatin dynamics during interphase, including replication in S phase, is crucial. We provide the current view concerning the centromeric architecture associated with satellite repeat sequences in mammals and its dynamics during the cell cycle...
January 31, 2017: Nature Reviews. Genetics
https://www.readbyqxmd.com/read/28138017/the-histone-chaperone-nrp1-interacts-with-werewolf-to-activate-glabra2-in-arabidopsis-root-hair-development
#8
Yan Zhu, Liang Rong, Qiang Luo, Baihui Wang, Nana Zhou, Yue Yang, Chi Zhang, Haiyang Feng, Lina Zheng, Wen-Hui Shen, Jinbiao Ma, Aiwu Dong
Nucleosome Assembly Protein 1 (NAP1) defines an evolutionarily conserved family of histone chaperones and loss-of-function of the Arabidopsis thaliana NAP1-family genes NAP1-RELATED PROTEIN 1 (NRP1) and NRP2 causes abnormal root hair formation. Yet, the underlying molecular mechanisms remain unclear. Here, we show that NRP1 interacts with the transcription factor WEREWOLF (WER) in vitro and in vivo and enriches at the GLABRA2 (GL2) promoter in a WER-dependent manner. Crystallographic analysis indicates that NRP1 forms a dimer via its N-terminal α-helix...
January 30, 2017: Plant Cell
https://www.readbyqxmd.com/read/28128545/single-molecule-investigations-on-histone-h2a-h2b-dynamics-in-the-nucleosome
#9
Jaehyoun Lee, Tae-Hee Lee
Nucleosomes impose physical barriers to DNA-templated processes, playing important roles in eukaryotic gene regulation. DNA is packaged into nucleosomes by histone proteins mainly through strong electrostatic interactions that can be modulated by various post-translational histone modifications. Investigating the dynamics of histone dissociation from the nucleosome and how it is altered upon histone modifications is important for understanding eukaryotic gene regulation mechanisms. In particular, histone H2A-H2B dimer displacement in the nucleosome is one of the most important and earliest steps of histone dissociation...
February 8, 2017: Biochemistry
https://www.readbyqxmd.com/read/28126821/rpa-binds-histone-h3-h4-and-functions-in-dna-replication-coupled-nucleosome-assembly
#10
Shaofeng Liu, Zhiyun Xu, He Leng, Pu Zheng, Jiayi Yang, Kaifu Chen, Jianxun Feng, Qing Li
DNA replication-coupled nucleosome assembly is essential to maintain genome integrity and retain epigenetic information. Multiple involved histone chaperones have been identified, but how nucleosome assembly is coupled to DNA replication remains elusive. Here we show that replication protein A (RPA), an essential replisome component that binds single-stranded DNA, has a role in replication-coupled nucleosome assembly. RPA directly binds free H3-H4. Assays using a synthetic sequence that mimics freshly unwound single-stranded DNA at replication fork showed that RPA promotes DNA-(H3-H4) complex formation immediately adjacent to double-stranded DNA...
January 27, 2017: Science
https://www.readbyqxmd.com/read/28123037/snasp-and-asf1a-function-through-both-competitive-and-compatible-modes-of-histone-binding
#11
Andrew Bowman, Akiko Koide, Jay S Goodman, Meaghan E Colling, Daria Zinne, Shohei Koide, Andreas G Ladurner
Histone chaperones are proteins that interact with histones to regulate the thermodynamic process of nucleosome assembly. sNASP and ASF1 are conserved histone chaperones that interact with histones H3 and H4 and are found in a multi-chaperoning complex in vivo Previously we identified a short peptide motif within H3 that binds to the TPR domain of sNASP with nanomolar affinity. Interestingly, this peptide motif is sequestered within the known ASF1-H3-H4 interface, raising the question of how these two proteins are found in complex together with histones when they share the same binding site...
January 25, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28123034/opposing-effects-of-valproic-acid-treatment-mediated-by-histone-deacetylase-inhibitor-activity-in-four-transgenic-x-laevis-models-of-retinitis-pigmentosa
#12
Ruanne Y J Vent-Schmidt, Runxia H Wen, Zusheng Zong, Colette N Chiu, Beatrice M Tam, Christopher G May, Orson L Moritz
: Retinitis pigmentosa (RP) is an inherited retinal degeneration (RD) that leads to blindness for which no treatment is available. RP is frequently caused by mutations in Rhodopsin; in some animal models, RD is exacerbated by light. Valproic acid (VPA) is a proposed treatment for RP and other neurodegenerative disorders, with a phase II trial for RP under way. However, the therapeutic mechanism is unclear, with minimal research supporting its use in RP. We investigated the effects of VPA on Xenopus laevis models of RP expressing human P23H, T17M, T4K, and Q344ter rhodopsins, which are associated with RP in humans...
January 25, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28107649/rpa-interacts-with-hira-and-regulates-h3-3-deposition-at-gene-regulatory-elements-in-mammalian-cells
#13
Honglian Zhang, Haiyun Gan, Zhiquan Wang, Jeong-Heon Lee, Hui Zhou, Tamas Ordog, Marc S Wold, Mats Ljungman, Zhiguo Zhang
The histone chaperone HIRA is involved in depositing histone variant H3.3 into distinct genic regions, including promoters, enhancers, and gene bodies. However, how HIRA deposits H3.3 to these regions remains elusive. Through a short hairpin RNA (shRNA) screening, we identified single-stranded DNA binding protein replication protein A (RPA) as a regulator of the deposition of newly synthesized H3.3 into chromatin. We show that RPA physically interacts with HIRA to form RPA-HIRA-H3.3 complexes, and it co-localizes with HIRA and H3...
January 19, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28094382/the-supercoiling-state-of-dna-determines-the-handedness-of-both-h3-and-cenp-a-nucleosomes
#14
R Vlijm, S H Kim, P L De Zwart, Y Dalal, C Dekker
Nucleosomes form the unit structure of the genome in eukaryotes, thereby constituting a fundamental tenet of chromatin biology. In canonical nucleosomes, DNA wraps around the histone octamer in a left-handed toroidal ramp. Here, in single-molecule magnetic tweezers studies of chaperone-assisted nucleosome assembly, we show that the handedness of the DNA wrapping around the nucleosome core is intrinsically ambidextrous, and depends on the pre-assembly supercoiling state of the DNA, i.e., it is not uniquely determined by the octameric histone core...
January 17, 2017: Nanoscale
https://www.readbyqxmd.com/read/28079009/emerging-roles-of-calreticulin-in-cancer-implications-for-therapy
#15
Kavya Venkateswaran, Amit Verma, Anant Narayan Bhatt, Anju Shrivastava, Kailash Manda, Hanumantharao G Raj, Ashok Prasad, Christophe Len, Virinder S Parmar, Bilikere Dwarakanath
Calreticulin (CRT), initially identified as a ubiquitous calcium-binding protein in the endoplasmic reticulum, has emerged as a multifunctional protein with roles in calcium homeostasis, molecular chaperoning and cell adhesion. Emerging evidence suggests its involvement in tumorigenesis facilitating proliferation, migration, and adhesion. CRT translocated to the cell surface (ecto-CRT) serves as a phagocytic signal for immunogenic cell death (ICD) mediated through dendritic cells (DCs) and cytotoxic T-cell activation thereby making tumors susceptible to immunotherapy-based anti-cancer strategies...
11, 2017: Current Protein & Peptide Science
https://www.readbyqxmd.com/read/28059702/cdk-regulated-dimerization-of-m18bp1-on-a-mis18-hexamer-is-necessary-for-cenp-a-loading
#16
Dongqing Pan, Kerstin Klare, Arsen Petrovic, Annika Take, Kai Walstein, Priyanka Singh, Arnaud Rondelet, Alexander W Bird, Andrea Musacchio
Centromeres are unique chromosomal loci that promote the assembly of kinetochores, macromolecular complexes that bind spindle microtubules during mitosis. In most organisms, centromeres lack defined genetic features. Rather, they are specified epigenetically by a centromere-specific histone H3 variant, CENP-A. The Mis18 complex, comprising the Mis18α:Mis18β subcomplex and M18BP1, is crucial for CENP-A homeostasis. It recruits the CENP-A-specific chaperone HJURP to centromeres and primes it for CENP-A loading...
January 6, 2017: ELife
https://www.readbyqxmd.com/read/28053344/histone-chaperone-networks-shaping-chromatin-function
#17
REVIEW
Colin M Hammond, Caroline B Strømme, Hongda Huang, Dinshaw J Patel, Anja Groth
The association of histones with specific chaperone complexes is important for their folding, oligomerization, post-translational modification, nuclear import, stability, assembly and genomic localization. In this way, the chaperoning of soluble histones is a key determinant of histone availability and fate, which affects all chromosomal processes, including gene expression, chromosome segregation and genome replication and repair. Here, we review the distinct structural and functional properties of the expanding network of histone chaperones...
March 2017: Nature Reviews. Molecular Cell Biology
https://www.readbyqxmd.com/read/28028239/asymmetric-unwrapping-of-nucleosomal-dna-propagates-asymmetric-opening-and-dissociation-of-the-histone-core
#18
Yujie Chen, Joshua M Tokuda, Traci Topping, Steve P Meisburger, Suzette A Pabit, Lisa M Gloss, Lois Pollack
The nucleosome core particle (NCP) is the basic structural unit for genome packaging in eukaryotic cells and consists of DNA wound around a core of eight histone proteins. DNA access is modulated through dynamic processes of NCP disassembly. Partly disassembled structures, such as the hexasome (containing six histones) and the tetrasome (four histones), are important for transcription regulation in vivo. However, the pathways for their formation have been difficult to characterize. We combine time-resolved (TR) small-angle X-ray scattering and TR-FRET to correlate changes in the DNA conformations with composition of the histone core during salt-induced disassembly of canonical NCPs...
January 10, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28025045/a-novel-role-for-nhp6-proteins-in-histone-gene-regulation-in-saccharomyces-cerevisiae
#19
Diletta Durano, Andrea Lukacs, Francesca Di Felice, Gioacchino Micheli, Giorgio Camilloni
Maintaining a stable and balanced histone pool is of paramount importance for genome stability and fine regulation of DNA replication and transcription. This involves a complex regulatory machinery, exploiting transcription factors as well as histone chaperones, chromatin remodelers and modifiers. The functional details of this machinery are as yet unclear. Previous studies report histone decrease in mammalian and yeast HMGB family mutants. In this study we find that Nhp6 proteins, the S. cerevisiae HMGB1 homologues, control histone gene expression by affecting nucleosome stability at regulative regions of the histone clusters...
December 23, 2016: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/27989438/chromatin-controls-dna-replication-origin-selection-lagging-strand-synthesis-and-replication-fork-rates
#20
Christoph F Kurat, Joseph T P Yeeles, Harshil Patel, Anne Early, John F X Diffley
The integrity of eukaryotic genomes requires rapid and regulated chromatin replication. How this is accomplished is still poorly understood. Using purified yeast replication proteins and fully chromatinized templates, we have reconstituted this process in vitro. We show that chromatin enforces DNA replication origin specificity by preventing non-specific MCM helicase loading. Helicase activation occurs efficiently in the context of chromatin, but subsequent replisome progression requires the histone chaperone FACT (facilitates chromatin transcription)...
January 5, 2017: Molecular Cell
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