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https://www.readbyqxmd.com/read/28537572/understanding-nucleosome-dynamics-and-their-links-to-gene-expression-and-dna-replication
#1
REVIEW
William K M Lai, B Franklin Pugh
Advances in genomics technology have provided the means to probe myriad chromatin interactions at unprecedented spatial and temporal resolution. This has led to a profound understanding of nucleosome organization within the genome, revealing that nucleosomes are highly dynamic. Nucleosome dynamics are governed by a complex interplay of histone composition, histone post-translational modifications, nucleosome occupancy and positioning within chromatin, which are influenced by numerous regulatory factors, including general regulatory factors, chromatin remodellers, chaperones and polymerases...
May 24, 2017: Nature Reviews. Molecular Cell Biology
https://www.readbyqxmd.com/read/28535770/emerging-roles-of-chromatin-in-the-maintenance-of-genome-organization-and-function-in-plants
#2
REVIEW
Zaida Vergara, Crisanto Gutierrez
Chromatin is not a uniform macromolecular entity; it contains different domains characterized by complex signatures of DNA and histone modifications. Such domains are organized both at a linear scale along the genome and spatially within the nucleus. We discuss recent discoveries regarding mechanisms that establish boundaries between chromatin states and nuclear territories. Chromatin organization is crucial for genome replication, transcriptional silencing, and DNA repair and recombination. The replication machinery is relevant for the maintenance of chromatin states, influencing DNA replication origin specification and accessibility...
May 23, 2017: Genome Biology
https://www.readbyqxmd.com/read/28534629/synthetic-posttranslational-modifications-chemical-catalyst-driven-regioselective-histone-acylation-of-native-chromatin
#3
Yoshifumi Amamoto, Yuki Aoi, Nozomu Nagashima, Hiroki Suto, Daisuke Yoshidome, Yasuhiro Arimura, Akihisa Osakabe, Daiki Kato, Hitoshi Kurumizaka, Shigehiro A Kawashima, Kenzo Yamatsugu, Motomu Kanai
Posttranslational modifications (PTMs) of histones play an important role in the complex regulatory mechanisms governing gene transcription, and their dysregulation can cause diseases such as cancer. The lack of methods for site-selectively modifying native chromatin, however, limits our understanding of the functional roles of a specific histone PTM, not as a single mark, but in the intertwined PTM network. Here, we report a synthetic catalyst DMAP-SH (DSH), which activates chemically stable thioesters (including acetyl-CoA) under physiological conditions and transfers various acyl groups to the proximate amino groups...
May 23, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28529337/dynamic-chromatin-technologies-from-individual-molecules-to-epigenomic-regulation-in-cells
#4
REVIEW
Olivier Cuvier, Beat Fierz
The establishment and maintenance of chromatin states involves multiscale dynamic processes integrating transcription factor and multiprotein effector dynamics, cycles of chemical chromatin modifications, and chromatin structural organization. Recent developments in genomic technologies are emerging that are enabling a view beyond ensemble- and time-averaged properties and are revealing the importance of dynamic chromatin states for cell fate decisions, differentiation and reprogramming at the single-cell level...
May 22, 2017: Nature Reviews. Genetics
https://www.readbyqxmd.com/read/28526911/dynamics-of-post-translationally-modified-histones-during-barley-pollen-embryogenesis-in-the-presence-or-absence-of-the-epi-drug-trichostatin-a
#5
Pooja Pandey, Diaa S Daghma, Andreas Houben, Jochen Kumlehn, Michael Melzer, Twan Rutten
Improving pollen embryogenesis. Despite the agro-economic importance of pollen embryogenesis, the mechanisms underlying this process are still poorly understood. We describe the dynamics of chromatin modifications (histones H3K4me2, H3K9ac, H3K9me2, and H3K27me3) and chromatin marks (RNA polymerase II CDC phospho-Ser5, and CENH3) during barley pollen embryogenesis. Immunolabeling results show that, in reaction to stress, immature pollen rapidly starts reorganizing several important chromatin modifications indicative of a change in cell fate...
May 19, 2017: Plant Reproduction
https://www.readbyqxmd.com/read/28526340/unfolding-the-pathogenesis-of-scleroderma-through-genomics-and-epigenomics
#6
REVIEW
Pei-Suen Tsou, Amr H Sawalha
With unknown etiology, scleroderma (SSc) is a multifaceted disease characterized by immune activation, vascular complications, and excessive fibrosis in internal organs. Genetic studies, including candidate gene association studies, genome-wide association studies, and whole-exome sequencing have supported the notion that while genetic susceptibility to SSc appears to be modest, SSc patients are genetically predisposed to this disease. The strongest genetic association for SSc lies within the MHC region, with loci in HLA-DRB1, HLA-DQB1, HLA-DPB1, and HLA-DOA1 being the most replicated...
May 16, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28525740/rnf8-and-ube2s-dependent-ubiquitin-lysine-11-linkage-modification-in-response-to-dna-damage
#7
Atanu Paul, Bin Wang
Ubiquitin modification of proteins plays pivotal roles in the cellular response to DNA damage. Given the complexity of ubiquitin conjugation due to the formation of poly-conjugates of different linkages, functional roles of linkage-specific ubiquitin modification at DNA damage sites are largely unclear. We identify that Lys11-linkage ubiquitin modification occurs at DNA damage sites in an ATM-dependent manner, and ubiquitin-modifying enzymes, including Ube2S E2-conjugating enzyme and RNF8 E3 ligase, are responsible for the assembly of Lys11-linkage conjugates on damaged chromatin, including histone H2A/H2AX...
May 18, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28524162/targeted-sequencing-based-analyses-of-candidate-gene-variants-in-ulcerative-colitis-associated-colorectal-neoplasia
#8
Sanjiban Chakrabarty, Vinay Koshy Varghese, Pranoy Sahu, Pradyumna Jayaram, Bhadravathi M Shivakumar, Cannanore Ganesh Pai, Kapaettu Satyamoorthy
BACKGROUND: Long-standing ulcerative colitis (UC) leading to colorectal cancer (CRC) is one of the most serious and life-threatening consequences acknowledged globally. Ulcerative colitis-associated colorectal carcinogenesis showed distinct molecular alterations when compared with sporadic colorectal carcinoma. METHODS: Targeted sequencing of 409 genes in tissue samples of 18 long-standing UC subjects at high risk of colorectal carcinoma (UCHR) was performed to identify somatic driver mutations, which may be involved in the molecular changes during the transformation of non-dysplastic mucosa to high-grade dysplasia...
May 18, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28523964/epigenetics-in-endometrial-carcinogenesis-part-2-histone-modifications-chromatin-remodeling-and-noncoding-rnas
#9
Carla Bartosch, José Manuel Lopes, Carmen Jerónimo
Carcinogenesis is a multistep multifactorial process that involves the accumulation of genetic and epigenetic alterations. In the past two decades, there has been an exponential growth of knowledge establishing the importance of epigenetic changes in cancer. Our work focused on reviewing the main role of epigenetics in the pathogenesis of endometrial carcinoma, highlighting the reported results concerning each epigenetic mechanistic layer. In a previous review, we assessed DNA methylation alterations. The present review examines the contribution of histone modifications, chromatin remodeling and noncoding RNA alterations for endometrial carcinogenesis...
May 19, 2017: Epigenomics
https://www.readbyqxmd.com/read/28523562/bioinformatics-tools-for-genome-wide-epigenetic-research
#10
Vladimir Espinosa Angarica, Antonio Del Sol
Epigenetics play a central role in the regulation of many important cellular processes, and dysregulations at the epigenetic level could be the source of serious pathologies, such as neurological disorders affecting brain development, neurodegeneration, and intellectual disability. Despite significant technological advances for epigenetic profiling, there is still a need for a systematic understanding of how epigenetics shapes cellular circuitry, and disease pathogenesis. The development of accurate computational approaches for analyzing complex epigenetic profiles is essential for disentangling the mechanisms underlying cellular development, and the intricate interaction networks determining and sensing chromatin modifications and DNA methylation to control gene expression...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28523552/epigenetics-of-huntington-s-disease
#11
Silvia Bassi, Takshashila Tripathi, Alan Monziani, Francesca Di Leva, Marta Biagioli
Huntington's disease (HD) is a genetic, fatal autosomal dominant neurodegenerative disorder typically occurring in midlife with symptoms ranging from chorea, to dementia, to personality disturbances (Philos Trans R Soc Lond Ser B Biol Sci 354:957-961, 1999). HD is inherited in a dominant fashion, and the underlying mutation in all cases is a CAG trinucleotide repeat expansion within exon 1 of the HD gene (Cell 72:971-983, 1993). The expanded CAG repeat, translated into a lengthened glutamine tract at the amino terminus of the huntingtin protein, affects its structural properties and functional activities...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28523551/epigenetic-mechanisms-of-gene-regulation-in-amyotrophic-lateral-sclerosis
#12
Alba Jimenez-Pacheco, Jaime M Franco, Soledad Lopez, Juan Miguel Gomez-Zumaquero, Maria Magdalena Leal-Lasarte, Diana E Caballero-Hernandez, Marta Cejudo-Guillén, David Pozo
Despite being clinically described 150 years ago, the mechanisms underlying amyotrophic lateral sclerosis (ALS) pathogenesis have not yet been fully understood. Studies in both animal models of ALS and human patients reveal a plethora of alterations such as increased glutamate-mediated excitotoxicity, redox stress, increased apoptosis, defective axonal transport, protein-misfolding events, mitochondrial impairment and sustained unregulated immune responses. Regardless of being sporadic or familiar ALS, the final outcome at the cellular level is the death of upper and lower motor neurons, and once diagnosed, ALS is typically lethal within the next 5 years...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28521327/epigenomics-pharmacoepigenomics-and-personalized-medicine-in-cervical-cancer
#13
Shama Prasada Kabekkodu, Sanjiban Chakrabarty, Supriti Ghosh, Angela Brand, Kapaettu Satyamoorthy
Epigenomics encompasses the study of genome-wide changes in DNA methylation, histone modifications and noncoding RNAs leading to altered transcription, chromatin structure, and posttranscription RNA processing, respectively, resulting in an altered rate of gene expression. The role of epigenetic modifications facilitating human diseases is well established. Previous studies have identified histone and cytosine code during normal and pathological conditions with special emphasis on how these modifications regulate transcriptional events...
May 19, 2017: Public Health Genomics
https://www.readbyqxmd.com/read/28520954/h2b-ubiquitylation-and-the-histone-chaperone-asf1-cooperatively-mediate-the-formation-and-maintenance-of-heterochromatin-silencing
#14
Meng-Ying Wu, Chia-Yeh Lin, Hsin-Yi Tseng, Fei-Man Hsu, Pao-Yang Chen, Cheng-Fu Kao
Heterochromatin is a heritable form of gene repression, with critical roles in development and cell identity. Understanding how chromatin factors results in such repression is a fundamental question. Chromatin is assembled and disassembled during transcription, replication and repair by anti-silencing function 1 (Asf1), a highly conserved histone chaperone. Transcription and DNA replication are also affected by histone modifications that modify nucleosome dynamics, such as H2B ubiquitylation (H2Bub). We report here that H2Bub and Asf1 cooperatively promote transcriptional silencing at yeast telomeres and mating loci...
May 17, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28520399/an-immunofluorescence-imaging-strategy-for-evaluation-of-the-accessibility-of-dna-5-hydroxymethylcytosine-in-chromatins
#15
Shangwei Zhong, Zhe Li, Ting Jiang, Xiangjun Li, Hailin Wang
DNA 5-hydroxymethylcytosine (5hmC) is an important epigenetic modification found in various mammalian cells. Immunofluorescence imaging analysis essentially provides visual pictures to the abundance and distribution of DNA 5hmC in single cells. However, nuclear DNA is usually wrapped around nucleosomes and packaged into chromatins, and further bound with many functional proteins. These physiologically relevant events would generate barriers to the anti-5hmC antibody to selectively recognize 5hmC in DNA. By taking advantage of these naturally generated barriers, here we present a strategy to evaluate the accessibility of DNA 5hmC in chromatins in situ...
May 18, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28516124/bioinformatic-analysis-for-profiling-drug-induced-chromatin-modification-landscapes-in-mouse-brain-using-chlp-seq-data
#16
Yong-Hwee Eddie Loh, Jian Feng, Eric Nestler, Li Shen
Chromatin immunoprecipitation followed by massively parallel sequencing (ChIP-seq) is a powerful technology to profile genome-wide chromatin modification patterns and is increasingly being used to study the molecular mechanisms of brain diseases such as drug addiction. This protocol discusses the typical procedures involved in ChIP-seq data generation, bioinformatic analysis, and interpretation of results, using a chronic cocaine treatment study as a template. We describe an experimental design that induces significant chromatin modifications in mouse brain, and the use of ChIP-seq to derive novel information about the chromatin regulatory mechanisms involved...
February 5, 2017: Bio-protocol
https://www.readbyqxmd.com/read/28515787/a-computational-approach-for-the-functional-classification-of-the-epigenome
#17
Francesco Gandolfi, Anna Tramontano
BACKGROUND: In the last decade, advanced functional genomics approaches and deep sequencing have allowed large-scale mapping of histone modifications and other epigenetic marks, highlighting functional relationships between chromatin organization and genome function. Here, we propose a novel approach to explore functional interactions between different epigenetic modifications and extract combinatorial profiles that can be used to annotate the chromatin in a finite number of functional classes...
2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/28514649/widespread-mitotic-bookmarking-by-histone-marks-and-transcription-factors-in-pluripotent-stem-cells
#18
Yiyuan Liu, Bobbie Pelham-Webb, Dafne Campigli Di Giammartino, Jiexi Li, Daleum Kim, Katsuhiro Kita, Nestor Saiz, Vidur Garg, Ashley Doane, Paraskevi Giannakakou, Anna-Katerina Hadjantonakis, Olivier Elemento, Effie Apostolou
During mitosis, transcription is halted and many chromatin features are lost, posing a challenge for the continuity of cell identity, particularly in fast cycling stem cells, which constantly balance self-renewal with differentiation. Here we show that, in pluripotent stem cells, certain histone marks and stem cell regulators remain associated with specific genomic regions of mitotic chromatin, a phenomenon known as mitotic bookmarking. Enhancers of stem cell-related genes are bookmarked by both H3K27ac and the master regulators OCT4, SOX2, and KLF4, while promoters of housekeeping genes retain high levels of mitotic H3K27ac in a cell-type invariant manner...
May 16, 2017: Cell Reports
https://www.readbyqxmd.com/read/28513600/temporal-dynamics-of-gene-expression-and-histone-marks-at-the-arabidopsis-shoot-meristem-during-flowering
#19
Yuan You, Aneta Sawikowska, Manuela Neumann, David Posé, Giovanna Capovilla, Tobias Langenecker, Richard A Neher, Paweł Krajewski, Markus Schmid
Plants can produce organs throughout their entire life from pluripotent stem cells located at their growing tip, the shoot apical meristem (SAM). At the time of flowering, the SAM of Arabidopsis thaliana switches fate and starts producing flowers instead of leaves. Correct timing of flowering in part determines reproductive success, and is therefore under environmental and endogenous control. How epigenetic regulation contributes to the floral transition has eluded analysis so far, mostly because of the poor accessibility of the SAM...
May 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/28507061/rnf8-mediates-histone-h3-ubiquitylation-and-promotes-glycolysis-and-tumorigenesis
#20
Yan Xia, Weiwei Yang, Ming Fa, Xinjian Li, Yugang Wang, Yuhui Jiang, Yanhua Zheng, Jong-Ho Lee, Jing Li, Zhimin Lu
Disassembly of nucleosomes in which genomic DNA is packaged with histone regulates gene expression. However, the mechanisms underlying nucleosome disassembly for gene expression remain elusive. We show here that epidermal growth factor receptor activation results in the binding of the RNF8 forkhead-associated domain to pyruvate kinase M2-phosphorylated histone H3-T11, leading to K48-linked polyubiquitylation of histone H3 at K4 and subsequent proteasome-dependent protein degradation. In addition, H3 polyubiquitylation induces histone dissociation from chromatin, nucleosome disassembly, and binding of RNA polymerase II to MYC and CCND1 promoter regions for transcription...
May 15, 2017: Journal of Experimental Medicine
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