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Histone variants

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https://www.readbyqxmd.com/read/29145630/yaf9-subunit-of-the-nua4-and-swr1-complexes-targets-histone-h3k27ac-through-its-yeats-domain
#1
Brianna J Klein, Salar Ahmad, Kendra R Vann, Forest H Andrews, Zachary A Mayo, Gaelle Bourriquen, Joseph B Bridgers, Jinyong Zhang, Brian D Strahl, Jacques Côté, Tatiana G Kutateladze
Yaf9 is an integral part of the NuA4 acetyltransferase and the SWR1 chromatin remodeling complexes. Here, we show that Yaf9 associates with acetylated histone H3 with high preference for H3K27ac. The crystal structure of the Yaf9 YEATS domain bound to the H3K27ac peptide reveals that the sequence C-terminal to K27ac stabilizes the complex. The side chain of K27ac inserts between two aromatic residues, mutation of which abrogates the interaction in vitro and leads in vivo to phenotypes similar to YAF9 deletion, including loss of SWR1-dependent incorporation of variant histone H2A...
November 14, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29145618/the-histone-variant-h2a-z-promotes-initiation-of-meiotic-recombination-in-fission-yeast
#2
Shintaro Yamada, Kazuto Kugou, Da-Qiao Ding, Yurika Fujita, Yasushi Hiraoka, Hiroshi Murakami, Kunihiro Ohta, Takatomi Yamada
Meiotic recombination is initiated by programmed formation of DNA double strand breaks (DSBs), which are mainly formed at recombination hotspots. Meiotic DSBs require multiple proteins including the conserved protein Spo11 and its cofactors, and are influenced by chromatin structure. For example, local chromatin around hotspots directly impacts DSB formation. Moreover, DSB is proposed to occur in a higher-order chromatin architecture termed 'axis-loop', in which many loops protrude from cohesin-enriched axis...
November 14, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29138493/suppression-of-srcap-chromatin-remodelling-complex-and-restriction-of-lymphoid-lineage-commitment-by-pcid2
#3
Buqing Ye, Benyu Liu, Liuliu Yang, Guanling Huang, Lu Hao, Pengyan Xia, Shuo Wang, Ying Du, Xiwen Qin, Pingping Zhu, Jiayi Wu, Nobuo Sakaguchi, Junyan Zhang, Zusen Fan
Lymphoid lineage commitment is an important process in haematopoiesis, which forms the immune system to protect the host from pathogen invasion. However, how multipotent progenitors (MPP) switch into common lymphoid progenitors (CLP) or common myeloid progenitors (CMP) during this process remains elusive. Here we show that PCI domain-containing protein 2 (Pcid2) is highly expressed in MPPs. Pcid2 deletion in the haematopoietic system causes skewed lymphoid lineage specification. In MPPs, Pcid2 interacts with the Zinc finger HIT-type containing 1 (ZNHIT1) to block Snf2-related CREBBP activator protein (SRCAP) activity and prevents the deposition of histone variant H2A...
November 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/29138278/a-cytoplasmic-compass-is-necessary-for-cell-survival-and-triple-negative-breast-cancer-pathogenesis-by-regulating-metabolism
#4
Lu Wang, Clayton K Collings, Zibo Zhao, Kira Alia Cozzolino, Quanhong Ma, Kaiwei Liang, Stacy A Marshall, Christie C Sze, Rintaro Hashizume, Jeffrey Nicholas Savas, Ali Shilatifard
Mutations and translocations within the COMPASS (complex of proteins associated with Set1) family of histone lysine methyltransferases are associated with a large number of human diseases, including cancer. Here we report that SET1B/COMPASS, which is essential for cell survival, surprisingly has a cytoplasmic variant. SET1B, but not its SET domain, is critical for maintaining cell viability, indicating a novel catalytic-independent role of SET1B/COMPASS. Loss of SET1B or its unique cytoplasmic-interacting protein, BOD1, leads to up-regulation of expression of numerous genes modulating fatty acid metabolism, including ADIPOR1 (adiponectin receptor 1), COX7C, SDC4, and COQ7 Our detailed molecular studies identify ADIPOR1 signaling, which is inactivated in both obesity and human cancers, as a key target of SET1B/COMPASS...
November 14, 2017: Genes & Development
https://www.readbyqxmd.com/read/29137252/a-novel-mutation-r190h-in-the-at-hook-1-domain-of-mecp2-identified-in-an-atypical-rett-syndrome
#5
Xiao Zhou, Yuangao Liao, Miaojing Xu, Zhong Ji, Yunqi Xu, Liang Zhou, Xiaoming Wei, Peiqian Hu, Peng Han, Fanghan Yang, Suyue Pan, Yafang Hu
Background: Mutations in Methyl-CpG binding protein 2 (MECP2) have been identified as the disease-causing mutations in Rett Syndrome (RTT). However, no mutation in the AT-hook 1 domain of MECP2 has been reported in RTT yet. The function of AT-hook 1 domain of MECP2 has not been described either. Methods: The clinical and radiological features of a girl with progressive hyperactivity and loss of acquired linguistic and motor functions were presented. Next generation sequencing was used to screen the causative gene...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29133298/functional-redundancy-of-variant-and-canonical-histone-h3-lysine-9-modification-in-drosophila
#6
Taylor J R Penke, Daniel J McKay, Brian D Strahl, A Gregory Matera, Robert J Duronio
Histone post-translational modifications (PTMs) and differential incorporation of variant and canonical histones into chromatin are central modes of epigenetic regulation. Despite similar protein sequences, histone variants are enriched for different suites of PTMs compared to their canonical counterparts. For example, variant histone H3.3 occurs primarily in transcribed regions and is enriched for "active" histone PTMs like Lys9 acetylation (H3.3K9ac), whereas the canonical histone H3 is enriched for Lys9 methylation (H3K9me), which is found in transcriptionally silent heterochromatin...
November 13, 2017: Genetics
https://www.readbyqxmd.com/read/29117711/acetylation-regulates-thioredoxin-reductase-oligomerization-and-activity
#7
David Wright, Zaid Altaany, Yumin Bi, Zaccary Alperstein, Patrick O'Donoghue
TrxR1 is a cancer target and essential selenoprotein that defends the cell against reactive oxygen species and regulates cellular signaling and redox pathways. Previous cell-based studies correlated TrxR1 acetylation with modulated cellular reduction activity, yet the function of specific acetylation sites on TrxR1 remain unknown. We produced site-specifically acetylated TrxR1 variants that also contain selenocysteine (Sec). We demonstrated efficient high-fidelity protein synthesis with 22 different amino acids by simultaneous UAG codon reassignment to Nε-acetyl-lysine (acK) and UGA codon recoding to Sec...
November 8, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/29116202/acetylated-histone-variant-h2a-z-is-involved-in-the-activation-of-neo-enhancers-in-prostate-cancer
#8
Fátima Valdés-Mora, Cathryn M Gould, Yolanda Colino-Sanguino, Wenjia Qu, Jenny Z Song, Kylie M Taylor, Fabian A Buske, Aaron L Statham, Shalima S Nair, Nicola J Armstrong, James G Kench, Kenneth M L Lee, Lisa G Horvath, Minru Qiu, Alexei Ilinykh, Nicole S Yeo-Teh, David Gallego-Ortega, Clare Stirzaker, Susan J Clark
Acetylation of the histone variant H2A.Z (H2A.Zac) occurs at active promoters and is associated with oncogene activation in prostate cancer, but its role in enhancer function is still poorly understood. Here we show that H2A.Zac containing nucleosomes are commonly redistributed to neo-enhancers in cancer resulting in a concomitant gain of chromatin accessibility and ectopic gene expression. Notably incorporation of acetylated H2A.Z nucleosomes is a pre-requisite for activation of Androgen receptor (AR) associated enhancers...
November 7, 2017: Nature Communications
https://www.readbyqxmd.com/read/29110173/combination-treatment-with-docetaxel-and-histone-deacetylase-inhibitors-downregulates-androgen-receptor-signaling-in-castration-resistant-prostate-cancer
#9
Sang Eun Park, Ha-Gyeong Kim, Dong Eun Kim, Yoo Jung Jung, Yunlim Kim, Seong-Yun Jeong, Eun Kyung Choi, Jung Jin Hwang, Choung-Soo Kim
Backgrounds Since most patients with castration-resistant prostate cancer (CRPC) develop resistance to its standard therapy docetaxel, many studies have attempted to identify novel combination treatment to meet the large clinical unmet need. In this study, we examined whether histone deacetylase inhibitors (HDACIs) enhanced the effect of docetaxel on AR signaling in CRPC cells harboring AR and its splice variants. Methods HDACIs (vorinostat and CG200745) were tested for their ability to enhance the effects of docetaxel on cell viability and inhibition of AR signaling in CRPC 22Rv1 and VCaP cells by using CellTiter-Glo™ Luminescent cell viability assay, synergy index analysis and Western blotting...
November 7, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/29107533/h3-3-k27m-cooperates-with-trp53-loss-and-pdgfra-gain-in-mouse-embryonic-neural-progenitor-cells-to-induce-invasive-high-grade-gliomas
#10
Manav Pathania, Nicolas De Jay, Nicola Maestro, Ashot S Harutyunyan, Justyna Nitarska, Pirasteh Pahlavan, Stephen Henderson, Leonie G Mikael, Angela Richard-Londt, Ying Zhang, Joana R Costa, Steven Hébert, Sima Khazaei, Nisreen Samir Ibrahim, Javier Herrero, Antonella Riccio, Steffen Albrecht, Robin Ketteler, Sebastian Brandner, Claudia L Kleinman, Nada Jabado, Paolo Salomoni
Gain-of-function mutations in histone 3 (H3) variants are found in a substantial proportion of pediatric high-grade gliomas (pHGG), often in association with TP53 loss and platelet-derived growth factor receptor alpha (PDGFRA) amplification. Here, we describe a somatic mouse model wherein H3.3(K27M) and Trp53 loss alone are sufficient for neoplastic transformation if introduced in utero. H3.3(K27M)-driven lesions are clonal, H3K27me3 depleted, Olig2 positive, highly proliferative, and diffusely spreading, thus recapitulating hallmark molecular and histopathological features of pHGG...
November 13, 2017: Cancer Cell
https://www.readbyqxmd.com/read/29103092/stress-induced-oryza-sativa-ruvbl1a-is-dna-independent-atpase-and-unwinds-dna-duplex-in-3-to-5-direction
#11
Shabnam K Saifi, Nishat Passricha, Renu Tuteja, Narendra Tuteja
RuvB, a member of AAA+ (ATPases Associated with diverse cellular Activities) superfamily of proteins, is essential, highly conserved and multifunctional in nature as it is involved in DNA damage repair, mitotic assembly, switching of histone variants and assembly of telomerase core complex. RuvB family is widely studied in various systems such as Escherichia coli, yeast, human, Drosophila, Plasmodium falciparum and mouse, but not well studied in plants. We have studied the transcript level of rice homologue of RuvB gene (OsRuvBL1a) under various abiotic stress conditions, and the results suggest that it is upregulated under salinity, cold and heat stress...
November 4, 2017: Protoplasma
https://www.readbyqxmd.com/read/29099280/variant-histone-h2afv-reprograms-dna-methylation-during-early-zebrafish-development
#12
Bhavani Madakashira, Laura Corbett, Chi Zhang, Pier Paoli, John W Casement, Jelena Mann, Kirsten C Sadler, Derek A Mann
The DNA methylome is re-patterned during discrete phases of vertebrate development. In zebrafish, there are two waves of global DNA demethylation and re-methylation: the first occurs prior to gastrulation when the parental methylome is changed to the zygotic pattern and the second occurs after formation of the embryonic body axis, during organ specification. The occupancy of the histone variant H2A.Z and regions of DNA methylation are generally anti-correlated, and it has been proposed that H2A.Z restricts the boundaries of highly methylated regions...
November 3, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/29095668/sumo-modification-system-facilitates-the-exchange-of-histone-variant-h2a-z-2-at-dna-damage-sites
#13
Atsuhiko Fukuto, Masae Ikura, Tsuyoshi Ikura, Jiying Sun, Yasunori Horikoshi, Hiroki Shima, Kazuhiko Igarashi, Masayuki Kusakabe, Masahiko Harata, Naoki Horikoshi, Hitoshi Kurumizaka, Yoshiaki Kiuchi, Satoshi Tashiro
Histone exchange and histone post-translational modifications play important roles in the regulation of DNA metabolism, by re-organizing the chromatin configuration. We previously demonstrated that the histone variant H2A.Z-2 is rapidly exchanged at damaged sites after DNA double strand break induction in human cells. In yeast, the small ubiquitin-like modifier (SUMO) modification of H2A.Z is involved in the DNA damage response. However, whether the SUMO modification regulates the exchange of human H2A.Z-2 at DNA damage sites remains unclear...
November 2, 2017: Nucleus
https://www.readbyqxmd.com/read/29089515/chromatin-interaction-networks-revealed-unique-connectivity-patterns-of-broad-h3k4me3-domains-and-super-enhancers-in-3d-chromatin
#14
Asa Thibodeau, Eladio J Márquez, Dong-Guk Shin, Paola Vera-Licona, Duygu Ucar
Broad domain promoters and super enhancers are regulatory elements that govern cell-specific functions and harbor disease-associated sequence variants. These elements are characterized by distinct epigenomic profiles, such as expanded deposition of histone marks H3K27ac for super enhancers and H3K4me3 for broad domains, however little is known about how they interact with each other and the rest of the genome in three-dimensional chromatin space. Using network theory methods, we studied chromatin interactions between broad domains and super enhancers in three ENCODE cell lines (K562, MCF7, GM12878) obtained via ChIA-PET, Hi-C, and Hi-CHIP assays...
October 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29080249/concise-review-epigenetic-regulation-of-hematopoiesis-biological-insights-and-therapeutic-applications
#15
REVIEW
Chiara Antoniani, Oriana Romano, Annarita Miccio
Hematopoiesis is the process of blood cell formation starting from hematopoietic stem/progenitor cells (HSPCs). The understanding of regulatory networks involved in hematopoiesis and their impact on gene expression is crucial to decipher the molecular mechanisms that control hematopoietic development in physiological and pathological conditions, and to develop novel therapeutic strategies. An increasing number of epigenetic studies aim at defining, on a genome-wide scale, the cis-regulatory sequences (e.g., promoters and enhancers) used by human HSPCs and their lineage-restricted progeny at different stages of development...
October 28, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/29079444/temporal-regulation-of-chromatin-during-myoblast-differentiation
#16
REVIEW
Akihito Harada, Yasuyuki Ohkawa, Anthony N Imbalzano
The commitment to and execution of differentiation programmes involves a significant change in gene expression in the precursor cell to facilitate development of the mature cell type. In addition to being regulated by lineage-determining and auxiliary transcription factors that drive these changes, the structural status of the chromatin has a considerable impact on the transcriptional competence of differentiation-specific genes, which is clearly demonstrated by the large number of cofactors and the extraordinary complex mechanisms by which these genes become activated...
October 28, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/29077523/heterochromatin-and-dna-damage-repair-use-different-histone-variants-and-relax
#17
Zdravko J Lorković, Frédéric Berger
Repair of damaged DNA requires the activation of kinases, which in turn phosphorylate diverse proteins including histone H2A.X, an event conserved from yeast to human. By combining genetics, biochemical, and cytological approaches, we recently reported that, in addition to H2A.X, phosphorylation of histone variant H2A.W.7 is required for DNA damage response in Arabidopsis. This work provides direct evidence for the functional diversification of plant-specific H2A.W histone variants, which are tightly associated with heterochromatin...
October 30, 2017: Nucleus
https://www.readbyqxmd.com/read/29075360/turnover-of-histones-and-histone-variants-in-postnatal-rat-brain-effects-of-alcohol-exposure
#18
Nadia Rachdaoui, Ling Li, Belinda Willard, Takhar Kasumov, Stephen Previs, Dipak Sarkar
BACKGROUND: Alcohol consumption during pregnancy is a significant public health problem and can result in a continuum of adverse outcomes to the fetus known as fetal alcohol spectrum disorders (FASD). Subjects with FASD show significant neurological deficits, ranging from microencephaly, neurobehavioral, and mental health problems to poor social adjustment and stress tolerance. Neurons are particularly sensitive to alcohol exposure. The neurotoxic action of alcohol, i.e., through ROS production, induces DNA damage and neuronal cell death by apoptosis...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/29074736/molecular-basis-of-cenp-c-association-with-the-cenp-a-nucleosome-at-yeast-centromeres
#19
Hua Xiao, Feng Wang, Jan Wisniewski, Alexey K Shaytan, Rodolfo Ghirlando, Peter C FitzGerald, Yingzi Huang, Debbie Wei, Shipeng Li, David Landsman, Anna R Panchenko, Carl Wu
Histone CENP-A-containing nucleosomes play an important role in nucleating kinetochores at centromeres for chromosome segregation. However, the molecular mechanisms by which CENP-A nucleosomes engage with kinetochore proteins are not well understood. Here, we report the finding of a new function for the budding yeast Cse4/CENP-A histone-fold domain interacting with inner kinetochore protein Mif2/CENP-C. Strikingly, we also discovered that AT-rich centromere DNA has an important role for Mif2 recruitment. Mif2 contacts one side of the nucleosome dyad, engaging with both Cse4 residues and AT-rich nucleosomal DNA...
October 26, 2017: Genes & Development
https://www.readbyqxmd.com/read/29074395/epigenetics-of-malignant-melanoma
#20
REVIEW
Bruce Moran, Romina Silva, Antoinette S Perry, William M Gallagher
Patients with malignant melanoma generally have a good prognosis if the disease presents prior to metastasis. Due to progress with targeted and immunotherapies, the median survival of metastatic melanoma patients is now over 2 years. The disease is characterised by one of the highest somatic mutation rates observed amongst cancer types, with a specific mutational signature based on UV radiation damage evident. Highly prevalent mutations, such as the BRAF(V600E), in the MAPK cascade indicate truncal involvement of this pathway in the earliest stage of melanoma...
October 23, 2017: Seminars in Cancer Biology
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