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Chromatin structure regulation

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https://www.readbyqxmd.com/read/29237752/ser7-of-rnapii-ctd-facilitates-heterochromatin-formation-by-linking-ncrna-to-rnai
#1
Takuya Kajitani, Hiroaki Kato, Yuji Chikashige, Chihiro Tsutsumi, Yasushi Hiraoka, Hiroshi Kimura, Yasuyuki Ohkawa, Chikashi Obuse, Damien Hermand, Yota Murakami
Some long noncoding RNAs (ncRNAs) transcribed by RNA polymerase II (RNAPII) are retained on chromatin, where they regulate RNAi and chromatin structure. The molecular basis of this retention remains unknown. We show that in fission yeast serine 7 (Ser7) of the C-terminal domain (CTD) of RNAPII is required for efficient siRNA generation for RNAi-dependent heterochromatin formation. Surprisingly, Ser7 facilitates chromatin retention of nascent heterochromatic RNAs (hRNAs). Chromatin retention of hRNAs and siRNA generation requires both Ser7 and an RNA-binding activity of the chromodomain of Chp1, a subunit of the RNA-induced transcriptional silencing (RITS) complex...
December 13, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29237741/liberating-cohesin-from-cohesion
#2
REVIEW
Kerry Bloom
Cohesin was identified through its major role in holding sister chromatids together. We are learning through analysis of cohesin and other members of the protein family (SMC [structural maintenance of chromosomes]) and their regulators that these ring complexes contribute to chromosome organization and dynamics throughout the cell cycle. We need to consider not only how ring complexes are regulated but how they interact with their fluctuating chromatin substrate.
November 1, 2017: Genes & Development
https://www.readbyqxmd.com/read/29234012/structural-basis-for-genome-wide-recognition-of-5-bp-gc-motifs-by-smad-transcription-factors
#3
Pau Martin-Malpartida, Marta Batet, Zuzanna Kaczmarska, Regina Freier, Tiago Gomes, Eric Aragón, Yilong Zou, Qiong Wang, Qiaoran Xi, Lidia Ruiz, Angela Vea, José A Márquez, Joan Massagué, Maria J Macias
Smad transcription factors activated by TGF-β or by BMP receptors form trimeric complexes with Smad4 to target specific genes for cell fate regulation. The CAGAC motif has been considered as the main binding element for Smad2/3/4, whereas Smad1/5/8 have been thought to preferentially bind GC-rich elements. However, chromatin immunoprecipitation analysis in embryonic stem cells showed extensive binding of Smad2/3/4 to GC-rich cis-regulatory elements. Here, we present the structural basis for specific binding of Smad3 and Smad4 to GC-rich motifs in the goosecoid promoter, a nodal-regulated differentiation gene...
December 12, 2017: Nature Communications
https://www.readbyqxmd.com/read/29233856/structure-of-the-arabidopsis-jmj14-h3k4me3-complex-provides-insight-into-the-substrate-specificity-of-kdm5-subfamily-histone-demethylases
#4
Zhenlin Yang, Qi Qiu, Wei Chen, Bei Jia, Xiaomei Chen, Hongmiao Hu, Kaixuan He, Xian Deng, Sisi Li, W Andy Tao, XiaoFeng Cao, Jiamu Du
In chromatin, histone methylation affects the epigenetic regulation of multiple processes in animals and plants and is modulated by the activities of histone methyltransferases and histone demethylases. The jumonji domain-containing histone demethylases have diverse functions and can be classified into several subfamilies. In humans, the jumonji domain-containing Lysine (K)-Specific Demethylase 5/Jumonji and ARID Domain Protein (KDM5/JARID) subfamily demethylases are specific for histone 3 lysine 4 trimethylation (H3K4me3) and are important drug targets for cancer treatment...
December 12, 2017: Plant Cell
https://www.readbyqxmd.com/read/29229852/regulatory-networks-specifying-cortical-interneurons-from-human-embryonic-stem-cells-reveal-roles-for-chd2-in-interneuron-development
#5
Kesavan Meganathan, Emily M A Lewis, Paul Gontarz, Shaopeng Liu, Edouard G Stanley, Andrew G Elefanty, James E Huettner, Bo Zhang, Kristen L Kroll
Cortical interneurons (cINs) modulate excitatory neuronal activity by providing local inhibition. During fetal development, several cIN subtypes derive from the medial ganglionic eminence (MGE), a transient ventral telencephalic structure. While altered cIN development contributes to neurodevelopmental disorders, the inaccessibility of human fetal brain tissue during development has hampered efforts to define molecular networks controlling this process. Here, we modified protocols for directed differentiation of human embryonic stem cells, obtaining efficient, accelerated production of MGE-like progenitors and MGE-derived cIN subtypes with the expected electrophysiological properties...
December 11, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29229750/profiling-of-accessible-chromatin-regions-across-multiple-plant-species-and-cell-types-reveals-common-gene-regulatory-principles-and-new-control-modules
#6
Kelsey A Maher, Marko Bajic, Kaisa Kajala, Mauricio Reynoso, Germain Pauluzzi, Donnelly West, Kristina Zumstein, Margaret Woodhouse, Kerry L Bubb, Michael W Dorrity, Christine Queitsch, Julia Bailey-Serres, Neelima Sinha, Siobhan M Brady, Roger Deal
The transcriptional regulatory structure of plant genomes remains poorly defined relative to animals. It is unclear how many cis-regulatory elements exist, where these elements lie relative to promoters, and how these features are conserved across plant species. We employed the Assay for Transposase-Accessible Chromatin (ATAC-seq) in four plant species (Arabidopsis thaliana, Medicago truncatula, Solanum lycopersicum, and Oryza sativa) to delineate open chromatin regions and transcription factor (TF) binding sites across each genome...
December 11, 2017: Plant Cell
https://www.readbyqxmd.com/read/29227354/current-views-on-the-pathogenesis-of-sjgren-s-syndrome
#7
Elena Pontarini, Davide Lucchesi, Michele Bombardieri
PURPOSE OF REVIEW: The purpose of this review is to provide an insight into the pathophysiological mechanisms involved in the pathogenesis of primary Sjgren's Syndrome (pSS), highlighting recent findings with potential therapeutic repercussions. RECENT FINDINGS: In the last 2 years, epigenetic analyses provided new insights into pSS pathogenesis. Characterization of DNA methylation patterns, chromatin structures and microRNA confirmed the importance of aberrant interferon and B-cell responses in the development of the disease...
December 8, 2017: Current Opinion in Rheumatology
https://www.readbyqxmd.com/read/29222118/purine-and-pyrimidine-triple-helix-forming-oligonucleotides-recognize-qualitatively-different-target-sites-at-the-ribosomal-dna-locus
#8
Rodrigo Maldonado, Michael Filarsky, Ingrid Grummt, Gernot Längst
Triplexes are non-canonical DNA structures, which are functionally associated with regulation of gene expression through ncRNA targeting to chromatin. Based on the rules of Hoogsteen base pairing, poly-purine sequences of a duplex can potentially form triplex structures with single-stranded oligonucleotides. Prediction of triplex-forming sequences by bioinformatics analyses have revealed enrichment of potential triplex targeting sites (TTS) at regulatory elements, mainly in promoters and enhancers, suggesting a potential function of RNA-DNA triplexes in transcriptional regulation...
December 8, 2017: RNA
https://www.readbyqxmd.com/read/29217590/a-mechanism-of-cohesin-dependent-loop-extrusion-organizes-zygotic-genome-architecture
#9
Johanna Gassler, Hugo B Brandão, Maxim Imakaev, Ilya M Flyamer, Sabrina Ladstätter, Wendy A Bickmore, Jan-Michael Peters, Leonid A Mirny, Kikuë Tachibana
Fertilization triggers assembly of higher-order chromatin structure from a condensed maternal and a naïve paternal genome to generate a totipotent embryo. Chromatin loops and domains have been detected in mouse zygotes by single-nucleus Hi-C (snHi-C), but not bulk Hi-C. It is therefore unclear when and how embryonic chromatin conformations are assembled. Here, we investigated whether a mechanism of cohesin-dependent loop extrusion generates higher-order chromatin structures within the one-cell embryo. Using snHi-C of mouse knockout embryos, we demonstrate that the zygotic genome folds into loops and domains that critically depend on Scc1-cohesin and that are regulated in size and linear density by Wapl...
December 7, 2017: EMBO Journal
https://www.readbyqxmd.com/read/29215703/design-synthesis-and-characterization-of-%C3%AE-%C3%AE-unsaturated-carboxylic-acid-and-its-urea-based-derivatives-that-explores-novel-epigenetic-modulators-in-human-non-small-cell-lung-cancer-a549-cell-line
#10
Anusha Chidambaram, S H Kavya, Ramesh Kumar Chidambaram, Rajasekaran Subbiah, John Marshal Jayaraj, Karthikeyan Muthusamy, Ravikumar Vilwanathan
Histone deacetylase inhibitors (HDACi) are a small molecule chemotherapeutics that target the chromatin remodeling through the regulation of histone and non-histone proteins. These inhibitors directed against HDAC enzymes have become an important therapeutic tool in oncology; consequently, scientific efforts have fortified the quest for newer and novel HDACi, which forces the design of structurally innovative HDACi. Various urea containing compounds exhibited admirable anticancer activity. On the basis of these observations, we design and synthesize HDAC specific blocker molecules which are specifically besieged towards class I, class II and class IV HDAC isoforms to enhance the structural assortment for HDACi...
December 7, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29211718/pirna-mediated-regulation-of-transposon-alternative-splicing-in-the-soma-and-germ-line
#11
Felipe Karam Teixeira, Martyna Okuniewska, Colin D Malone, Rémi-Xavier Coux, Donald C Rio, Ruth Lehmann
Transposable elements can drive genome evolution, but their enhanced activity is detrimental to the host and therefore must be tightly regulated. The Piwi-interacting small RNA (piRNA) pathway is vital for the regulation of transposable elements, by inducing transcriptional silencing or post-transcriptional decay of mRNAs. Here we show that piRNAs and piRNA biogenesis components regulate precursor mRNA splicing of P-transposable element transcripts in vivo, leading to the production of the non-transposase-encoding mature mRNA isoform in Drosophila germ cells...
December 6, 2017: Nature
https://www.readbyqxmd.com/read/29211711/kat2a-coupled-with-the-%C3%AE-kgdh-complex-acts-as-a-histone-h3-succinyltransferase
#12
Yugang Wang, Yusong R Guo, Ke Liu, Zheng Yin, Rui Liu, Yan Xia, Lin Tan, Peiying Yang, Jong-Ho Lee, Xin-Jian Li, David Hawke, Yanhua Zheng, Xu Qian, Jianxin Lyu, Jie He, Dongming Xing, Yizhi Jane Tao, Zhimin Lu
Histone modifications, such as the frequently occurring lysine succinylation, are central to the regulation of chromatin-based processes. However, the mechanism and functional consequences of histone succinylation are unknown. Here we show that the α-ketoglutarate dehydrogenase (α-KGDH) complex is localized in the nucleus in human cell lines and binds to lysine acetyltransferase 2A (KAT2A, also known as GCN5) in the promoter regions of genes. We show that succinyl-coenzyme A (succinyl-CoA) binds to KAT2A...
December 6, 2017: Nature
https://www.readbyqxmd.com/read/29209909/biochemical-and-biophysical-characterisation-of-higher-oligomeric-structure-of-rat-nucleosome-assembly-protein-1
#13
Divya Reddy, Saikat Bhattacharya, Vinod Jani, Uddhavesh Sonavane, Rajendra Joshi, Sanjay Gupta
Nucleosome assembly protein 1 (NAP1) is a histone chaperone that exchanges histone H2A-H2B dimer from chromatin templates. Studies with yeast NAP1 (yNAP1) have revealed its existence as multiple oligomeric species in solution. Here, rat NAP1 (rNAP1), which is 98% identical to the human NAP1 (hNAP1) was used as a model to characterize the oligomeric structures of this protein in higher eukaryotes. Gel filtration chromatography and Dynamic light scattering of recombinant rNAP1 indicated that the protein exists as a complex mixture of multimeric species even at 500 mM ionic strength...
December 5, 2017: Protein Journal
https://www.readbyqxmd.com/read/29206861/preparative-two-step-purification-of-recombinant-h1-0-linker-histone-and-its-domains
#14
Nives Ivic, Silvija Bilokapic, Mario Halic
H1 linker histones are small basic proteins that have a key role in the formation and maintenance of higher-order chromatin structures. Additionally, many examples have shown that linker histones play an important role in gene regulation, modulated by their various subtypes and posttranslational modifications. Obtaining high amounts of very pure linker histones, especially for efficient antibody production, remains a demanding and challenging procedure. Here we present an easy and fast method to purify human linker histone H1...
2017: PloS One
https://www.readbyqxmd.com/read/29206178/around-and-beyond-53bp1-nuclear-bodies
#15
REVIEW
Anne Fernandez-Vidal, Julien Vignard, Gladys Mirey
Within the nucleus, sub-nuclear domains define territories where specific functions occur. Nuclear bodies (NBs) are dynamic structures that concentrate nuclear factors and that can be observed microscopically. Recently, NBs containing the p53 binding protein 1 (53BP1), a key component of the DNA damage response, were defined. Interestingly, 53BP1 NBs are visualized during G1 phase, in daughter cells, while DNA damage was generated in mother cells and not properly processed. Unlike most NBs involved in transcriptional processes, replication has proven to be key for 53BP1 NBs, with replication stress leading to the formation of these large chromatin domains in daughter cells...
December 5, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29202635/the-coupled-effect-of-nucleosome-organization-on-gene-transcription-level-and-transcriptional-plasticity
#16
Jian Chen, EnLi, Jinsheng Lai
Nucleosomes are the fundamental units of eukaryotic chromatin and can modulate the DNA accessibility for transcriptional regulatory elements. Many studies have demonstrated the effect of nucleosome organization on gene transcription level and transcriptional plasticity upon different conditions. Our recent study showed that nucleosome organization also plays an important role in modulating the plasticity of gene transcriptional status in maize. Here, we integrated our findings with previous studies on the role of nucleosome organization in regulation of gene transcription...
December 5, 2017: Nucleus
https://www.readbyqxmd.com/read/29199022/ctcf-mediated-chromatin-loops-between-promoter-and-gene-body-regulate-alternative-splicing-across-individuals
#17
Mariana Ruiz-Velasco, Manjeet Kumar, Mang Ching Lai, Pooja Bhat, Ana Belen Solis-Pinson, Alejandro Reyes, Stefan Kleinsorg, Kyung-Min Noh, Toby J Gibson, Judith B Zaugg
The CCCTC-binding factor (CTCF) is known to establish long-range DNA contacts that alter the three-dimensional architecture of chromatin, but how the presence of CTCF influences nearby gene expression is still poorly understood. Here, we analyze CTCF chromatin immunoprecipitation sequencing, RNA sequencing, and Hi-C data, together with genotypes from a healthy human cohort, and measure statistical associations between inter-individual variability in CTCF binding and alternative exon usage. We demonstrate that CTCF-mediated chromatin loops between promoters and intragenic regions are prevalent and that when exons are in physical proximity with their promoters, CTCF binding correlates with exon inclusion in spliced mRNA...
November 24, 2017: Cell Systems
https://www.readbyqxmd.com/read/29196662/toehold-enhanced-lna-probes-for-selective-pull-down-and-single-molecule-analysis-of-native-chromatin
#18
Nicolaas Hermans, Juriën Jori Huisman, Thomas Bauke Brouwer, Christopher Schächner, G Paul H van Heusden, Joachim Griesenbeck, John van Noort
The organization of DNA into chromatin is thought to regulate gene expression in eukaryotes. To study its structure in vitro, there is a need for techniques that can isolate specific chromosomal loci of natively assembled chromatin. Current purification methods often involve chemical cross-linking to preserve the chromatin composition. However, such cross-linking may affect the native structure. It also impedes single molecule force spectroscopy experiments, which have been instrumental to probe chromatin folding...
December 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29196562/the-role-of-bromodomain-and-extraterminal-motif-bet-proteins-in-chromatin-structure
#19
Sarah C Hsu, Gerd A Blobel
Bromodomain and extraterminal motif (BET) proteins have been widely investigated for their roles in gene regulation and their potential as therapeutic targets in cancer. Pharmacologic BET inhibitors target the conserved bromodomain-acetyllysine interaction and do not distinguish between BRD2, BRD3, and BRD4. Thus, comparatively little is known regarding the distinct roles played by individual family members, as well as the underlying mechanisms that drive the transcriptional effects of BET inhibitors. Here we review studies regarding the contributions of BET proteins to genome structure and function, including recent work identifying a role for BRD2 as a component of functional and physical chromatin domain boundaries...
December 1, 2017: Cold Spring Harbor Symposia on Quantitative Biology
https://www.readbyqxmd.com/read/29187422/dependency-of-heterochromatin-domains-on-replication-factors
#20
Leonie Johanna Jahn, Bethany Mason, Peter Brøgger, Tea Toteva, Dennis Kim Nielsen, Genevieve Thon
Chromatin structure regulates both genome expression and dynamics in eukaryotes where large heterochromatic regions are epigenetically silenced through the methylation of histone H3K9, histone deacetylation, and assembly of repressive complexes. Previous genetic screens with the fission yeast Schizosaccharomyces pombe have led to the identification of key enzymatic activities and structural constituents of heterochromatin. We report here on additional factors discovered by screening a library of deletion mutants for silencing defects at the edge of a heterochromatic domain bound by its natural boundary - the IR-R+ element - or by ectopic boundaries...
November 29, 2017: G3: Genes—Genomes—Genetics
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