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https://www.readbyqxmd.com/read/28549169/regulatory-dynamics-of-11p13-suggest-a-role-for-ehf-in-modifying-cf-lung-disease-severity
#1
Lindsay R Stolzenburg, Rui Yang, Jenny L Kerschner, Sara Fossum, Matthew Xu, Andrew Hoffmann, Kay-Marie Lamar, Sujana Ghosh, Sarah Wachtel, Shih-Hsing Leir, Ann Harris
Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene cause cystic fibrosis (CF), but are not good predictors of lung phenotype. Genome-wide association studies (GWAS) previously identified additional genomic sites associated with CF lung disease severity. One of these, at chromosome 11p13, is an intergenic region between Ets homologous factor (EHF) and Apaf-1 interacting protein (APIP). Our goal was to determine the functional significance of this region, which being intergenic is probably regulatory...
May 26, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28546430/crosstalk-between-the-h3k36me3-and-h4k16ac-histone-epigenetic-marks-in-dna-double-strand-break-repair
#2
Lin Li, Yinsheng Wang
Post-translational modifications of histone proteins regulate numerous cellular processes. Among these modifications, trimethylation of lysine 36 in histone H3 (H3K36me3) and acetylation of lysine 16 in histone H4 (H4K16ac) have important roles in transcriptional regulation and DNA damage response signaling. However, whether these two epigenetic histone marks are mechanistically linked remains unclear. Here, we discovered a new pathway through which H3K36me3 stimulates H4K16ac upon DNA double-strand break (DSB) induction in human cells...
May 25, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28545024/an-unusual-intragenic-promoter-of-piwil2-contributes-to-aberrant-activation-of-oncogenic-pl2l60
#3
Shan-Shan Liu, Ning Liu, Meng-Yao Liu, Lei Sun, Wu-Yan Xia, Hong-Min Lu, Yu-Jie Fu, Guo-Liang Yang, Juan-Jie Bo, Xiao-Xing Liu, Haizhong Feng, Hailong Wu, Lin-Feng Li, Jian-Xin Gao
PIWIL2-like (PL2L) protein 60 (PL2L60), a product of aberrantly activated PIWIL2 gene, is widely expressed in various types of tumors and may promote tumorigenesis. However, the mechanisms underlying the activation of expression of PL2L60 remain unknown. In this study, an intragenic promoter responsible for the activation of PL2L60 within the human PIWIL2 gene has been identified, cloned and characterized. The promoter of PL2L60 is located in the intron 10 of the host gene PIWIL2. Bioinformatic and mutagenic analysis reveals that this intragenic promoter within the sequence of 50 nucleotides contains two closely arranged cis-acting elements specific for the hepatic leukemia factor (HLF) in the positive strand and signal transducer and activator of transcription 3 (STAT3) in the negative strand...
May 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28544931/role-for-rif1-interacting-partner-ddx1-in-blm-recruitment-to-dna-double-strand-breaks
#4
Lei Li, Ho-Yin Poon, Matthew R Hildebrandt, Elizabeth A Monckton, Devon R Germain, Richard P Fahlman, Roseline Godbout
Human Rap1-interacting factor 1 (RIF1) is an important player in the repair of DNA double strand breaks (DSBs). RIF1 acts downstream of 53BP1, with well-documented roles in class switch recombination in B-cells and inhibition of end resection initiation in BRCA1-defective cells. Here, we report that DEAD Box 1 (DDX1), a RNA helicase also implicated in DSB repair, interacts with RIF1, with co-localization of DDX1 and RIF1 observed throughout interphase. Recruitment of DDX1 to DSBs is dependent on RIF1, with RIF1 depletion abolishing DDX1-mediated facilitation of homologous recombination at DSBs...
May 13, 2017: DNA Repair
https://www.readbyqxmd.com/read/28542146/the-role-of-extracellular-histone-in-organ-injury
#5
REVIEW
Eleanor Silk, Hailin Zhao, Hao Weng, Daqing Ma
Histones are intra-nuclear cationic proteins that are present in all eukaryotic cells and are highly conserved across species. Within the nucleus, they provide structural stability to chromatin and regulate gene expression. Histone may be released into the extracellular space in three forms: freely, as a DNA-bound nucleosome or as part of neutrophil extracellular traps, and all three can be detected in serum after significant cellular death such as sepsis, trauma, ischaemia/reperfusion injury and autoimmune disease...
May 25, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28539971/a-fast-efficient-chromatin-immunoprecipitation-method-for-studying-protein-dna-binding-in-arabidopsis-mesophyll-protoplasts
#6
Jeong Hwan Lee, Suhyun Jin, Sun Young Kim, Wanhui Kim, Ji Hoon Ahn
BACKGROUND: Binding of transcription factors to their target sequences is a primary step in the regulation of gene expression and largely determines gene regulatory networks. Chromatin immunoprecipitation (ChIP) is an indispensable tool used to investigate the binding of DNA-binding proteins (e.g., transcription factors) to their target sequences in vivo. ChIP assays require specific antibodies that recognize endogenous target transcription factors; however, in most cases, such specific antibodies are unavailable...
2017: Plant Methods
https://www.readbyqxmd.com/read/28537572/understanding-nucleosome-dynamics-and-their-links-to-gene-expression-and-dna-replication
#7
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/28537551/rna-dependent-chromatin-association-of-transcription-elongation-factors-and-pol-ii-ctd-kinases
#8
Sofia Battaglia, Michael Lidschreiber, Carlo Baejen, Phillipp Torkler, Seychelle M Vos, Patrick Cramer
For transcription through chromatin, RNA polymerase (Pol) II associates with elongation factors (EFs). Here we show that many EFs crosslink to RNA emerging from transcribing Pol II in the yeast Saccharomyces cerevisiae. Most EFs crosslink preferentially to mRNAs, rather than unstable non-coding RNAs. RNA contributes to chromatin association of many EFs, including the Pol II serine 2 kinases Ctk1 and Bur1 and the histone H3 methyltransferases Set1 and Set2. The Ctk1 kinase complex binds RNA in vitro, consistent with direct EF-RNA interaction...
May 24, 2017: ELife
https://www.readbyqxmd.com/read/28536180/yy1-and-ctcf-orchestrate-a-3d-chromatin-looping-switch-during-early-neural-lineage-commitment
#9
Jonathan A Beagan, Michael T Duong, Katelyn R Titus, Linda Zhou, Zhendong Cao, Jingjing Ma, Caroline V Lachanski, Daniel R Gillis, Jennifer E Phillips-Cremins
CTCF is an architectural protein with a critical role in connecting higher-order chromatin folding in pluripotent stem cells. Recent reports have suggested that CTCF binding is more dynamic during development than previously appreciated. Here we set out to understand the extent to which shifts in genome-wide CTCF occupancy contribute to the 3-D reconfiguration of fine-scale chromatin folding during early neural lineage commitment. Unexpectedly, we observe a sharp decrease in CTCF occupancy during the transition from naive/primed pluripotency to multipotent primary neural progenitor cells (NPCs)...
May 23, 2017: Genome Research
https://www.readbyqxmd.com/read/28534629/synthetic-posttranslational-modifications-chemical-catalyst-driven-regioselective-histone-acylation-of-native-chromatin
#10
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/28534509/a-novel-interaction-of-pak4-with-ppar%C3%AE-to-regulate-nox1-and-radiation-induced-epithelial-to-mesenchymal-transition-in-glioma
#11
D Kesanakurti, D Maddirela, Y K Banasavadi-Siddegowda, T-H Lai, Z Qamri, N K Jacob, D Sampath, S Mohanam, B Kaur, V K Puduvalli
Tumor recurrence in glioblastoma (GBM) is, in part, attributed to increased epithelial-to-mesenchymal transition (EMT) and enhanced tumor cell dissemination in adjacent brain parenchyma after ionizing radiation (IR). EMT is associated with aggressive behavior, increased stem-like characteristics and treatment resistance in malignancies; however, the underlying signaling mechanisms that regulate EMT are poorly understood. We identified grade-dependent p21-activated kinases 4 (PAK4) upregulation in gliomas and further determined its role in mesenchymal transition and radioresistance...
May 22, 2017: Oncogene
https://www.readbyqxmd.com/read/28533407/histone-binding-of-dpf2-mediates-its-repressive-role-in-myeloid-differentiation
#12
Ferdinand M Huber, Sarah M Greenblatt, Andrew M Davenport, Concepcion Martinez, Ye Xu, Ly P Vu, Stephen D Nimer, André Hoelz
Double plant homeodomain finger 2 (DPF2) is a highly evolutionarily conserved member of the d4 protein family that is ubiquitously expressed in human tissues and was recently shown to inhibit the myeloid differentiation of hematopoietic stem/progenitor and acute myelogenous leukemia cells. Here, we present the crystal structure of the tandem plant homeodomain finger domain of human DPF2 at 1.6-Å resolution. We show that DPF2 interacts with the acetylated tails of both histones 3 and 4 via bipartite binding pockets on the DPF2 surface...
May 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28531944/upregulation-of-ccat2-promotes-cell-proliferation-by-repressing-the-p15-in-breast-cancer
#13
Xin Deng, Yi Zhao, Xin Wu, Guoqing Song
BACKGROUND: Long non-coding RNAs (lncRNAs) are demonstrated to function as modulators of both transcriptional and post-transcriptional regulation in various types of tumors progression. The objective of the study is to investigate the clinical significance and underlying mechanism of Colon cancer associated transcript 2 (CCAT2) involved in breast cancer. METHODS: QT-PCR was performed to examine the relative expression levels of CCAT2 in breast cancer tissues and adjacent normal tissues...
May 17, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28529706/expresso-a-database-and-web-server-for-exploring-the-interaction-of-transcription-factors-and-their-target-genes-in-arabidopsis-thaliana-using-chip-seq-peak-data
#14
Delasa Aghamirzaie, Karthik Raja Velmurugan, Shuchi Wu, Doaa Altarawy, Lenwood S Heath, Ruth Grene
Motivation: The increasing availability of chromatin immunoprecipitation sequencing (ChIP-Seq) data enables us to learn more about the action of transcription factors in the regulation of gene expression. Even though in vivo transcriptional regulation often involves the concerted action of more than one transcription factor, the format of each individual ChIP-Seq dataset usually represents the action of a single transcription factor. Therefore, a relational database in which available ChIP-Seq datasets are curated is essential...
2017: F1000Research
https://www.readbyqxmd.com/read/28529100/transcriptional-and-post-transcriptional-gene-regulation-by-long-non-coding-rna
#15
REVIEW
Iain Dykes, Costanza Emanueli
Advances in genomics technology over recent years have led to the surprising discovery that the genome is far more pervasively transcribed than was previously appreciated. Much of the newly-discovered transcriptome appears to represent long non-coding RNA (lncRNA), a heterogeneous group of largely uncharacterised transcripts. Understanding the biological function of these molecules represents a major challenge and in this review we discuss some of the progress made to date. One major theme of lncRNA biology seems to be the existence of a network of interactions with microRNA (miRNA) pathways...
May 18, 2017: Genomics, Proteomics & Bioinformatics
https://www.readbyqxmd.com/read/28529057/structural-basis-for-the-versatile-and-methylation-dependent-binding-of-ctcf-to-dna
#16
Hideharu Hashimoto, Dongxue Wang, John R Horton, Xing Zhang, Victor G Corces, Xiaodong Cheng
The multidomain CCCTC-binding factor (CTCF), containing a tandem array of 11 zinc fingers (ZFs), modulates the three-dimensional organization of chromatin. We crystallized the human CTCF DNA-binding domain in complex with a known CTCF-binding site. While ZF2 does not make sequence-specific contacts, each finger of ZF3-7 contacts three bases of the 15-bp consensus sequence. Each conserved nucleotide makes base-specific hydrogen bonds with a particular residue. Most of the variable base pairs within the core sequence also engage in interactions with the protein...
May 15, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28528781/capsid-dependent-host-factors-in-hiv-1-infection
#17
REVIEW
Masahiro Yamashita, Alan N Engelman
After invasion of a susceptible target cell, HIV-1 completes the early phase of its life cycle upon integration of reverse-transcribed viral DNA into host chromatin. The viral capsid, a conical shell encasing the viral ribonucleoprotein complex, along with its constitutive capsid protein, plays essential roles at virtually every step in the early phase of the viral life cycle. Recent work has begun to reveal how the viral capsid interacts with specific cellular proteins to promote these processes. At the same time, cellular restriction factors target the viral capsid to thwart infection...
May 18, 2017: Trends in Microbiology
https://www.readbyqxmd.com/read/28528697/an-embryonic-stem-cell-specific-nurd-complex-functions-through-interaction-with-wdr5
#18
Ly-Sha Ee, Kurtis N McCannell, Yang Tang, Nancy Fernandes, W Rod Hardy, Michael R Green, Feixia Chu, Thomas G Fazzio
The Nucleosome Remodeling and Deacetylase (NuRD) complex is a chromatin regulatory complex that functions as a transcriptional co-repressor in metazoans. The NuRD subunit MBD3 is essential for targeting and assembly of a functional NuRD complex as well as embryonic stem cell (ESC) pluripotency. Three MBD3 isoforms (MBD3A, MBD3B, and MBD3C) are expressed in mouse. Here, we find that the MBD3C isoform contains a unique 50-amino-acid N-terminal region that is necessary for MBD3C to specifically interact with the histone H3 binding protein WDR5...
May 17, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28528689/human-papillomaviruses-in-epigenetic-regulations
#19
REVIEW
Julia Durzynska, Krzysztof Lesniewicz, Elzbieta Poreba
Human Papillomaviruses (HPVs) are double-stranded DNA viruses, that infect epithelial cells and are etiologically involved in the development of human cancer. Today, over 200 types of human papillomaviruses are known. They are divided into low-risk and high-risk HPVs depending on their potential to induce carcinogenesis, driven by two major viral oncoproteins, E6 and E7. By interacting with cellular partners, these proteins are involved in interdependent viral and cell cycles in stratified differentiating epithelium, and concomitantly induce epigenetic changes in infected cells and those undergoing malignant transformation...
April 2017: Mutation Research
https://www.readbyqxmd.com/read/28526829/super-enhancers-and-broad-h3k4me3-domains-form-complex-gene-regulatory-circuits-involving-chromatin-interactions
#20
Fan Cao, Yiwen Fang, Hong Kee Tan, Yufen Goh, Jocelyn Yeen Hui Choy, Bryan Thean Howe Koh, Jiong Hao Tan, Nicolas Bertin, Aroul Ramadass, Ewan Hunter, Jayne Green, Matthew Salter, Alexandre Akoulitchev, Wilson Wang, Wee Joo Chng, Daniel G Tenen, Melissa J Fullwood
Stretched histone regions, such as super-enhancers and broad H3K4me3 domains, are associated with maintenance of cell identity and cancer. We connected super-enhancers and broad H3K4me3 domains in the K562 chronic myelogenous leukemia cell line as well as the MCF-7 breast cancer cell line with chromatin interactions. Super-enhancers and broad H3K4me3 domains showed higher association with chromatin interactions than their typical counterparts. Interestingly, we identified a subset of super-enhancers that overlap with broad H3K4me3 domains and show high association with cancer-associated genes including tumor suppressor genes...
May 19, 2017: Scientific Reports
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