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https://www.readbyqxmd.com/read/28820351/genomic-and-chromatin-features-shaping-meiotic-double-strand-break-formation-and-repair-in-mice
#1
Shintaro Yamada, Seoyoung Kim, Sam E Tischfield, Maria Jasin, Julian Lange, Scott Keeney
The SPO11-generated DNA double-strand breaks (DSBs) that initiate meiotic recombination occur non-randomly across genomes, but mechanisms shaping their distribution and repair remain incompletely understood. Here, we expand on recent studies of nucleotide-resolution DSB maps in mouse spermatocytes. We find that trimethylation of histone H3 lysine 36 around DSB hotspots is highly correlated, both spatially and quantitatively, with trimethylation of H3 lysine 4, consistent with coordinated formation and action of both PRDM9-dependent histone modifications...
August 18, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28820331/polo-like-kinase-1-plk1-dependent-phosphorylation-of-methylenetetrahydrofolate-reductase-mthfr-regulates-replication-via-histone-methylation
#2
Xueyan Li, Shanshan Nai, Yuehe Ding, Qizhi Geng, Bingtao Zhu, Kai Yu, Wei-Guo Zhu, Meng-Qiu Dong, Xiao-Dong Su, Xingzhi Xu, Jing Li
Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme regulating the folate cycle and its genetic variations have been associated with various human diseases. Previously we identified that MTHFR is phosphorylated by cyclin-dependent kinase 1 (CDK1) at T34 and MTHFR underlies heterochromatin maintenance marked by H3K9me3 levels. Herein we demonstrate that pT34 creates a binding motif that docks MTHFR to the polo-binding domain (PBD) of polo-like kinase 1 (PLK1), a fundamental kinase that orchestrates many cell cycle events...
August 18, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28819432/silencing-of-hjurp-induces-dysregulation-of-cell-cycle-and-ros-metabolism-in-bladder-cancer-cells-via-ppar%C3%AE-sirt1-feedback-loop
#3
Rui Cao, Gang Wang, Kaiyu Qian, Liang Chen, Guofeng Qian, Conghua Xie, Han C Dan, Wei Jiang, Min Wu, Chin-Lee Wu, Yu Xiao, Xinghuan Wang
Holliday Junction Recognition Protein (HJURP) is a centromeric histone chaperone involving in de novo histone H3 variant CenH3 (CENP-A) recruitment. Our transcriptome and in vivo study revealed that HJURP is significantly upregulated in bladder cancer (BCa) tissues at both mRNA and protein levels. Knockdown of HJURP inhibited proliferation and viability of BCa cell lines revealed by CCK-8, colony formation and Ki-67-staining assays, and induced apoptosis and reactive oxygen species (ROS) production, as well as triggered cell cycle arrest at G0/G1 phase possibly via loss of CENP-A...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28819127/multiple-e3s-promote-the-degradation-of-histone-h3-variant-cse4
#4
Haili Cheng, Xin Bao, Xin Gan, Shiwen Luo, Hai Rao
The histone H3-like protein Cse4/CENP-A acts as a key molecular marker that differentiates the special centromeric chromatin structures from bulk nucleosomes. As altered Cse4/CENP-A activity leads to genome instability, it is pivotal to understand the mechanism underlying Cse4 regulation. Here, we demonstrate that four ubiquitin ligases (i.e., Ubr1, Slx5, Psh1, and Rcy1) work in parallel to promote Cse4 turnover in yeast. Interestingly, Cse4 overexpression leads to cellular toxicity and cell cycle delay in yeast cells lacking PSH1, but not in cells lacking UBR1, suggesting different roles of these two degradation pathways...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28818970/dna-replication-coupled-histone-modification-maintains-polycomb-gene-silencing-in-plants
#5
Danhua Jiang, Frédéric Berger
Propagation of patterns of gene expression through the cell cycle requires prompt restoration of epigenetic marks after the twofold dilution caused by DNA replication. Here, we show that the transcriptional repressive mark histone H3 lysine 27 trimethylation (H3K27me3) is restored in replicating plant cells through DNA replication-coupled modification of histone variant H3.1. Plants evolved a mechanism for efficient K27 trimethylation on H3.1, which is essential for inheritance of the silencing memory from mother to daughter cells...
August 17, 2017: Science
https://www.readbyqxmd.com/read/28816574/sgt1-hsp90-complex-is-required-for-cenp-a-deposition-at-centromeres
#6
Yohei Niikura, Risa Kitagawa, Hiroo Ogi, Katsumi Kitagawa
The centromere plays an essential role in accurate chromosome segregation, and defects in its function lead to aneuploidy and thus cancer. The centromere-specific histone H3 variant CENP-A is proposed to be the epigenetic mark of the centromere, as active centromeres require CENP-A-containing nucleosomes to direct the recruitment of multiple kinetochore proteins. CENP-A K124 ubiquitylation, mediated by CUL4A-RBX1-COPS8 E3 ligase activity, is required for CENP-A deposition at the centromere. However, the mechanism that controls the E3 ligase activity of the CUL4A-RBX1-COPS8 complex remains obscure...
August 17, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28803373/th2a-is-phosphorylated-at-meiotic-centromere-by-haspin
#7
Masashi Hada, Jihye Kim, Erina Inoue, Yuko Fukuda, Hiromitsu Tanaka, Yoshinori Watanabe, Yuki Okada
Histone phosphorylation is sometimes associated with mitosis and meiosis. We have recently identified a phosphorylation of the 127th threonine on TH2A (pTH2A), a germ cell-specific H2A variant, in condensed spermatids and mitotic early preimplantation embryos of mice. Here, we further report the existence of pTH2A at the centromeres in metaphase I spermatocytes and oocytes. Moreover, we identified Haspin, a known kinase for the 3rd threonine on H3, is responsible for pTH2A in vivo. In contrast to the severe meiotic defect in oocytes treated with a Haspin inhibitor, pTH2A-deficient mice, in which the 127th threonine was replaced by alanine, maintained the fertility and exhibited no obvious defect in both oocytes and spermatogenesis...
August 12, 2017: Chromosoma
https://www.readbyqxmd.com/read/28791511/centromere-inheritance-through-the-germline
#8
REVIEW
Arunika Das, Evan M Smoak, Ricardo Linares-Saldana, Michael A Lampson, Ben E Black
The centromere directs chromosome segregation and genetic inheritance but is not itself heritable in a canonical, DNA-based manner. In most species, centromeres are epigenetically defined by the presence of a histone H3 variant centromere protein A (CENP-A), independent of underlying DNA sequence. Therefore, centromere inheritance depends on maintaining the CENP-A nucleosome mark across generations. Experiments in cycling somatic cells have led to a model in which centromere identity is maintained by a cell cycle-coupled CENP-A chromatin assembly pathway...
August 8, 2017: Chromosoma
https://www.readbyqxmd.com/read/28790150/phosphorylation-of-histone-h2a-at-serine-95-a-plant-specific-mark-involved-in-flowering-time-regulation-and-h2a-z-deposition
#9
Yanhua Su, Shiliang Wang, Fei Zhang, Han Zheng, Yana Liu, Tongtong Huang, Yong Ding
Phosphorylation of histone H3 affects transcription, chromatin condensation, and chromosome segregation. However, the role of phosphorylation of histone H2A remains unclear. Here, we found that Arabidopsis thaliana MUT9P-LIKE-KINASE (MLK4) phosphorylates histone H2A on serine 95, a plant-specific modification in the histone core domain. Mutations in MLK4 caused late flowering under long-day conditions but no notable phenotype under short days. MLK4 interacts with CIRCADIAN CLOCK ASSOCIATED1 (CCA1), which allows MLK4 to bind to the GIGANTEA (GI) promoter...
August 8, 2017: Plant Cell
https://www.readbyqxmd.com/read/28781076/epigenetic-reprogramming-of-lineage-committed-human-mammary-epithelial-cells-requires-dnmt3a-and-loss-of-dot1l
#10
Jerrica L Breindel, Adam Skibinski, Maja Sedic, Ania Wronski-Campos, Wenhui Zhou, Patricia J Keller, Joslyn Mills, James Bradner, Tamer Onder, Charlotte Kuperwasser
Organogenesis and tissue development occur through sequential stepwise processes leading to increased lineage restriction and loss of pluripotency. An exception to this appears in the adult human breast, where rare variant epithelial cells exhibit pluripotency and multilineage differentiation potential when removed from the signals of their native microenvironment. This phenomenon provides a unique opportunity to study mechanisms that lead to cellular reprogramming and lineage plasticity in real time. Here, we show that primary human mammary epithelial cells (HMECs) lose expression of differentiated mammary epithelial markers in a manner dependent on paracrine factors and epigenetic regulation...
July 25, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28775067/running-training-experience-attenuates-disuse-atrophy-in-fast-twitch-skeletal-muscles-of-rats
#11
Keisuke Nakamura, Ikumi Ohsawa, Ryo Masuzawa, Ryotaro Konno, Atsuya Watanabe, Fuminori Kawano
Responsiveness to physiological stimuli, such as exercise and muscular inactivation, differs in individuals. However, the mechanisms responsible for these individual differences remain poorly understood. We tested whether a prior experience of exercise training affects the responses of skeletal muscles to unloading. Young rats were assigned to perform daily running training using a treadmill for 8 weeks. After an additional 8 weeks of normal habitation, the rats were hindlimb unloaded by tail suspension for 1 week...
August 3, 2017: Journal of Applied Physiology
https://www.readbyqxmd.com/read/28771339/specific-acetylation-patterns-of-h2a-z-form-transient-interactions-with-the-bptf-bromodomain
#12
Gabriella T Perell, Neeraj K Mishra, Babu Sudhamalla, Peter D Ycas, Kabirul Islam, William C K Pomerantz
Post-translational lysine acetylation of histone tails affect both chromatin accessibility and recruitment of multi-functional bromodomain-containing proteins for modulating transcription. Bromodomain and PHD finger-containing protein (BPTF) regulates transcription, but has also been implicated with high gene expression levels in a variety of cancers. In this report, the histone variant H2A.Z, which replaces H2A in chromatin, is evaluated for affinity towards BPTF with a specific recognition pattern of acetylated lysine residues of the N-terminal tail region...
August 3, 2017: Biochemistry
https://www.readbyqxmd.com/read/28768200/cfp1-regulates-histone-h3k4-trimethylation-and-developmental-potential-in-mouse-oocytes
#13
Chao Yu, Xiaoying Fan, Qian-Qian Sha, Hui-Han Wang, Bo-Tai Li, Xing-Xing Dai, Li Shen, Junping Liu, Lie Wang, Kui Liu, Fuchou Tang, Heng-Yu Fan
Trimethylation of histone H3 at lysine-4 (H3K4me3) is associated with eukaryotic gene promoters and poises their transcriptional activation during development. To examine the in vivo function of H3K4me3 in the absence of DNA replication, we deleted CXXC finger protein 1 (CFP1), the DNA-binding subunit of the SETD1 histone H3K4 methyltransferase, in developing oocytes. We find that CFP1 is required for H3K4me3 accumulation and the deposition of histone variants onto chromatin during oocyte maturation. Decreased H3K4me3 in oocytes caused global downregulation of transcription activity...
August 1, 2017: Cell Reports
https://www.readbyqxmd.com/read/28765161/the-interplay-between-epigenetic-changes-and-the-p53-protein-in-stem-cells
#14
REVIEW
Arnold J Levine, Shelley L Berger
Epigenetic programs regulate the development and maintenance of organisms over a lifetime. These programs are carried out through chemical modifications of DNA and proteins such as histones and transcription factors. These epigenetic modifications are less stable than genetic alterations and even reversible under a variety of circumstances, such as developmental changes, regeneration of tissues, cell divisions, aging, and pathological conditions observed in many cancers. The p53 protein not only enforces the stability of the genome by the prevention of genetic alterations in cells but also plays a role in regulating the epigenetic changes that can occur in cells...
June 15, 2017: Genes & Development
https://www.readbyqxmd.com/read/28760857/fbw7-loss-promotes-chromosomal-instability-and-tumorigenesis-via-cyclin-e1-cdk2-mediated-phosphorylation-of-cenp-a
#15
Mamoru Takada, Weiguo Zhang, Aussie Suzuki, Taruho Kuroda, Zhouliang Yu, Hiroyuki Inuzuka, Daming Gao, Lixin Wan, Ming Zhuang, Lianxin Hu, Bo Zhai, Christopher Fry, Kerry Bloom, Guohong Li, Gary Karpen, Wenyi Wei, Qing Zhang
The centromere regulates proper chromosome segregation and its dysfunction is implicated in chromosomal instability (CIN). However, relatively little is known about how centromere dysfunction occurs in cancer. Here we define the consequences of phosphorylation by Cyclin E1/CDK2 on a conserved Ser18 residue of centromere-associated protein CENP-A, an essential histone H3 variant that specifies centromere identity. Ser18 hyperphosphorylation in cells occurred upon loss of FBW7, a tumor suppressor whose inactivation leads to chromosomal instability (CIN)...
July 31, 2017: Cancer Research
https://www.readbyqxmd.com/read/28758091/identifying-the-kat6b-mutation-via-diagnostic-exome-sequencing-to-diagnose-say-barber-biesecker-young-simpson-syndrome-in-three-generations-of-a-family
#16
Yong Rok Kim, Jong Bum Park, Yung Jin Lee, Mi Jin Hong, Hyeong Tae Kim, Hyon J Kim
Diagnostic exome sequencing (DES) is a powerful tool to analyze the pathogenic variants leading to development delay (DD) and intellectual disability (ID). Recently, heterozygous de novo mutation of the histone acetyltransferase encoding gene KAT6B has been recognized as causing a syndrome with congenital anomalies and intellectual disability, namely Say-Barber-Biesecker-Young-Simpson (SBBYS) syndrome. Here we report a case of SBBYS syndrome in a third generation Korean family affected with a missense mutation in KAT6B, c...
June 2017: Annals of Rehabilitation Medicine
https://www.readbyqxmd.com/read/28756949/expanded-satellite-repeats-amplify-a-discrete-cenp-a-nucleosome-assembly-site-on-chromosomes-that-drive-in-female-meiosis
#17
Aiko Iwata-Otsubo, Jennine M Dawicki-McKenna, Takashi Akera, Samantha J Falk, Lukáš Chmátal, Karren Yang, Beth A Sullivan, Richard M Schultz, Michael A Lampson, Ben E Black
Female meiosis provides an opportunity for selfish genetic elements to violate Mendel's law of segregation by increasing the chance of segregating to the egg [1]. Centromeres and other repetitive sequences can drive in meiosis by cheating the segregation process [2], but the underlying mechanisms are unknown. Here, we show that centromeres with more satellite repeats house more nucleosomes that confer centromere identity, containing the histone H3 variant CENP-A, and bias their segregation to the egg relative to centromeres with fewer repeats...
August 7, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28754822/epigenetic-research-in-multiple-sclerosis-progress-challenges-and-opportunities
#18
Galina Zheleznyakova, Eliane Piket, Francesco Marabita, Majid Pahlevan Kakhki, Ewoud Ewing, Sabrina Ruhrmann, Maria Needhamsen, Maja Jagodic, Lara Kular
Multiple Sclerosis (MS) is a chronic inflammatory and demyelinating disease of the central nervous system. MS likely results from a complex interplay between predisposing causal gene variants (the strongest influence coming from HLA class II locus) and environmental risk factors such as smoking, infectious mononucleosis and lack of sun exposure/vitamin D. However, little is known about the mechanisms underlying MS development and progression. Moreover, the clinical heterogeneity and variable response to treatment represent additional challenges to a comprehensive understanding and efficient treatment of disease...
July 28, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/28752458/measuring-the-effect-of-histone-deacetylase-inhibitors-hdaci-on-the-secretion-and-activity-of-alpha-1-antitrypsin
#19
Chao Wang, Marion Bouchecareilh, William E Balch
Alpha-1 antitrypsin deficiency (AATD) is a protein conformational disease with the most common cause being the Z-variant mutation in alpha-1 antitrypsin (Z-AAT). The misfolded conformation triggered by the Z-variant disrupts cellular proteostasis (protein folding) systems and fails to meet the endoplasmic reticulum (ER) export metrics, leading to decreased circulating AAT and deficient antiprotease activity in the plasma and lung. Here, we describe the methods for measuring the secretion and neutrophil elastase (NE) inhibition activity of AAT/Z-AAT, as well as the response to histone deacetylase inhibitor (HDACi), a major proteostasis modifier that impacts the secretion and function of AATD from the liver to plasma...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28746399/coordination-of-matrix-attachment-and-atp-dependent-chromatin-remodeling-regulate-auxin-biosynthesis-and-arabidopsis-hypocotyl-elongation
#20
Kyounghee Lee, Pil Joon Seo
Hypocotyl elongation is extensively controlled by hormone signaling networks. In particular, auxin metabolism and signaling play key roles in light-dependent hypocotyl growth. The nuclear matrix facilitates organization of DNA within the nucleus, and dynamic interactions between nuclear matrix and DNA are related to gene regulation. Conserved scaffold/matrix attachment regions (S/MARs) are anchored to the nuclear matrix by the AT-HOOK MOTIF CONTAINING NUCLEAR LOCALIZED (AHL) proteins in Arabidopsis. Here, we found that ESCAROLA (ESC)/AHL27 and SUPPRESSOR OF PHYTOCHROME B-4 #3 (SOB3)/AHL29 redundantly regulate auxin biosynthesis in the control of hypocotyl elongation...
2017: PloS One
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