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https://www.readbyqxmd.com/read/29334377/detecting-hierarchical-genome-folding-with-network-modularity
#1
Heidi K Norton, Daniel J Emerson, Harvey Huang, Jesi Kim, Katelyn R Titus, Shi Gu, Danielle S Bassett, Jennifer E Phillips-Cremins
Mammalian genomes are folded in a hierarchy of compartments, topologically associating domains (TADs), subTADs and looping interactions. Here, we describe 3DNetMod, a graph theory-based method for sensitive and accurate detection of chromatin domains across length scales in Hi-C data. We identify nested, partially overlapping TADs and subTADs genome wide by optimizing network modularity and varying a single resolution parameter. 3DNetMod can be applied broadly to understand genome reconfiguration in development and disease...
January 15, 2018: Nature Methods
https://www.readbyqxmd.com/read/29334242/development-and-disease-in-a-dish-the-epigenetics-of-neurodevelopmental-disorders
#2
Emily Ma Lewis, Kristen L Kroll
Human neurodevelopmental disorders (NDDs) involve mutations in hundreds of individual genes, with over-representation in genes encoding proteins that alter chromatin structure to modulate gene expression. Here, we highlight efforts to model these NDDs through in vitro differentiation of patient-specific induced pluripotent stem cells into neurons. We discuss how epigenetic regulation controls normal cortical development, how mutations in several classes of epigenetic regulators contribute to NDDs, and approaches for modeling cortical development and function using both directed differentiation and formation of cerebral organoids...
January 15, 2018: Epigenomics
https://www.readbyqxmd.com/read/29333723/nandrolone-induced-nuclear-accumulation-of-myod-protein-is-mediated-by-numb-a-notch-inhibitor-in-c2c12-myoblasts
#3
Xin-Hua Liu, Rita De Gasperi, William A Bauman, Christopher P Cardozo
Signaling via the androgen receptor (AR) stimulates myogenic progenitor differentiation. In addition, myogenic differentiation factor D (MyoD) and Numb, a Notch inhibitor, play key roles in regulating myogenic differentiation. Nandrolone, an anabolic steroid, upregulates both MyoD and Numb expression in myogenic cells. However, the molecular mechanisms by which MyoD is upregulated by nandrolone are unclear. Moreover, the potential crosstalk between nandrolone, MyoD, and Numb is not well understood. With these considerations in mind, we examined the effects of nandrolone on the expression of MyoD mRNA and protein, and determined the interactions of MyoD and Numb in the presence or absence of nandrolone in differentiating C2C12 myoblasts...
January 2018: Physiological Reports
https://www.readbyqxmd.com/read/29333204/aggressive-prostate-cancer-cell-nuclei-have-reduced-stiffness
#4
Zeina S Khan, Julianna M Santos, Fazle Hussain
It has been hypothesized that highly metastatic cancer cells have softer nuclei and hence would travel faster through confining environments. Our goal was to prove this untested hypothesis for prostate cells. Our nuclear creep experiments using a microfluidic channel with a narrow constriction show that stiffness of aggressive immortalized prostate cancer nuclei is significantly lower than that of immortalized normal cell nuclei and hence can be a convenient malignancy marker. Nuclear stiffness is found to be the highest for cells expressing high levels of lamin A/C but lowest for cells expressing low lamin A/C levels...
January 2018: Biomicrofluidics
https://www.readbyqxmd.com/read/29332916/mir-135a-promotes-inflammatory-responses-of-vascular-smooth-muscle-cells-from-db-db-mice-via-downregulation-of-foxo1
#5
Xiaochun Lu, Dawei Yin, Bo Zhou, Tieling Li
It has been shown that microRNAs (miRNAs) greatly affect the functions of vascular smooth muscle cells (VSMC), but the effects of mRNAs under diabetic conditions remain unclear.Using a model of diabetic db/db mice, we studied the functions of microRNA-135a (miR-135a) during VSMC dysfunction.Compared to control WT mice, miR-135a expression in VSMC was significantly increased while the level of forkhead box O1 (FOXO1) protein decreased significantly. After transfecting miR-135a mimics into VSMC, the expression of FOXO1 was decreased, while cyclooxygenase-2 (COX-2) and monocyte chemoattractant protein-1 (MCP-1) expression levels were increased, thus promoting the interaction between monocytes and WT VSMC...
January 15, 2018: International Heart Journal
https://www.readbyqxmd.com/read/29332353/aesculetin-6-7-dihydroxycoumarin-exhibits-potent-and-selective-antitumor-activity-in-human-acute-myeloid-leukemia-cells-thp-1-via-induction-of-mitochondrial-mediated-apoptosis-and-cancer-cell-migration-inhibition
#6
Jian Gong, Wei-Guo Zhang, Xiao-Fen Feng, Mei-Juan Shao, Chao Xing
PURPOSE: The main target of the present research was to examine the antitumor properties of aesculetin in human acute myeloid leukemia cancer cells (THP-1) and peripheral blood mono-nucleated cells (PBMCs) (used as normal cell line model) along with the determination of its effects on induction of apoptosis, inhibition of cancer cell migration and changes in Bcl-2/Bax protein expressions. METHODS: MTT colorimetric bioassay was performed to study the impact of this natural compound on cytotoxicity of both cell types...
November 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/29332283/markers-of-developmentally-regulated-programmed-cell-death-and-their-analysis-in-cereal-seeds
#7
Fernando Domínguez, Francisco Javier Cejudo
Programmed cell death (PCD) is a key process for the development and differentiation of multicellular organisms, which is characterized by well-defined morphological and biochemical features. These include chromatin condensation, DNA degradation and nuclear fragmentation, with nucleases and proteases playing a relevant function in these processes. In this chapter we describe methods routinely used for the analysis of hallmarks of developmentally regulated PCD in cereal seed tissues, which are based on agarose and polyacrylamide gel electrophoresis, in situ staining of DNA fragmentation, and cell-free assays of relevant enzymatic activities...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29332189/the-arabidopsis-histone-chaperone-fact-is-required-for-stress-induced-expression-of-anthocyanin-biosynthetic-genes
#8
Alexander Pfab, Matthias Breindl, Klaus D Grasser
The histone chaperone FACT is involved in the expression of genes encoding anthocyanin biosynthetic enzymes also upon induction by moderate high-light and therefore contributes to the stress-induced plant pigmentation. The histone chaperone FACT consists of the SSRP1 and SPT16 proteins and associates with transcribing RNAPII (RNAPII) along the transcribed region of genes. FACT can promote transcriptional elongation by destabilising nucleosomes in the path of RNA polymerase II, thereby facilitating efficient transcription of chromatin templates...
January 13, 2018: Plant Molecular Biology
https://www.readbyqxmd.com/read/29331085/verification-of-dna-motifs-in-arabidopsis-using-crispr-cas9-mediated-mutagenesis
#9
Chenlong Li, Chen Chen, Huhui Chen, Suikang Wang, Xuemei Chen, Yuhai Cui
Transcription factors (TFs) and chromatin-modifying factors (CMFs) access chromatin by recognizing specific DNA motifs in their target genes. Chromatin Immunoprecipitation followed by next generation sequencing (ChIP-seq) has been widely used to discover the potential DNA binding motifs for both TFs and CMFs. Yet, an in vivo method for verifying DNA motifs captured by ChIP-seq is lacking in plants. Here, we describe the use of clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated 9 (Cas9) to verify DNA motifs in their native genomic context in Arabidopsis...
January 13, 2018: Plant Biotechnology Journal
https://www.readbyqxmd.com/read/29330791/chromatin-immunoprecipitation-of-hif-%C3%AE-in-breast-tumor-cells-using-wild-type-and-loss-of-function-models
#10
Danielle L Brooks, Tiffany N Seagroves
Chromatin immunoprecipitation (ChIP) is a powerful method to determine whether a protein of interest binds to specific regulatory elements of the genome. Herein, we outline protocols optimized to detect binding of Hypoxia-Inducible Factor (HIF)-1α or HIF-2α to putative hypoxia response elements (HREs) within HIF target genes expressed in breast tumor epithelial cells.
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29330744/c-fos-downregulation-positively-regulates-epha5-expression-in-a-congenital-hypothyroidism-rat-model
#11
Honghua Song, Yuqin Zheng, Fuying Cai, Yanyan Ma, Jingyue Yang, Youjia Wu
The EphA5 receptor is well established as an axon guidance molecule during neural system development and plays an important role in dendritic spine formation and synaptogenesis. Our previous study has showed that EphA5 is decreased in the developing brain of congenital hypothyroidism (CH) and the EphA5 promoter methylation modification participates in its decrease. c-Fos, a well-kown transcription factor, has been considered in association with brain development. Bioinformatics analysis showed that the EphA5 promoter region contained five putative c-fos binding sites...
January 12, 2018: Journal of Molecular Histology
https://www.readbyqxmd.com/read/29330435/beta-catenin-cleavage-enhances-transcriptional-activation
#12
Tatiana Goretsky, Emily M Bradford, Qing Ye, Olivia F Lamping, Tomas Vanagunas, Mary Pat Moyer, Patrick C Keller, Preetika Sinh, Josep M Llovet, Tianyan Gao, Qing-Bai She, Linheng Li, Terrence A Barrett
Nuclear activation of Wnt/β-catenin signaling is required for cell proliferation in inflammation and cancer. Studies from our group indicate that β-catenin activation in colitis and colorectal cancer (CRC) correlates with increased nuclear levels of β-catenin phosphorylated at serine 552 (pβ-Cat552). Biochemical analysis of nuclear extracts from cancer biopsies revealed the existence of low molecular weight (LMW) pβ-Cat552, increased to the exclusion of full size (FS) forms of β-catenin. LMW β-catenin lacks both termini, leaving residues in the armadillo repeat intact...
January 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29330263/senescence-associated-chromatin-remodeling-promotes-cancer-stemness
#13
(no author information available yet)
Treatment-induced senescence is associated with stem-cell reprogramming of non-stem cancer cells.
January 12, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29330049/the-histone-demethylase-phf8-promotes-adult-acute-lymphoblastic-leukemia-through-interaction-with-the-mek-erk-signaling-pathway
#14
Yue Fu, Yaling Yang, Xiaoming Wang, Xiaolin Yin, Minran Zhou, Siqi Wang, Lin Yang, Tao Huang, Man Xu, Chunyan Chen
Adult acute lymphoblastic leukemia (ALL) is a malignant disorder of lymphoid progenitor cells that is associated with a high risk of relapse and poor prognosis. Thus, novel pathogenic mechanisms and therapeutic targets need to be explored. Histone methylation is one of the most significant chromatin post-translational modifications. Here, we show that the histone demethylase PHF8 is highly expressed in a large number of ALL clinical specimens and that PHF8 expression is associated with ALL progression. PHF8 knockdown inhibits proliferation and promotes the apoptosis of ALL cells in vitro as well as attenuates tumor growth in vivo...
January 9, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29329550/systematic-quantitative-analysis-of-h2a-and-h2b-variants-by-targeted-proteomics
#15
Sara El Kennani, Annie Adrait, Olga Permiakova, Anne-Marie Hesse, Côme Ialy-Radio, Myriam Ferro, Virginie Brun, Julie Cocquet, Jérôme Govin, Delphine Pflieger
BACKGROUND: Histones organize DNA into chromatin through a variety of processes. Among them, a vast diversity of histone variants can be incorporated into chromatin and finely modulate its organization and functionality. Classically, the study of histone variants has largely relied on antibody-based assays. However, antibodies have a limited efficiency to discriminate between highly similar histone variants. RESULTS: In this study, we established a mass spectrometry-based analysis to address this challenge...
January 12, 2018: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/29329517/genome-wide-analyses-of-direct-target-genes-of-four-rice-nac-domain-transcription-factors-involved-in-drought-tolerance
#16
Pil Joong Chung, Harin Jung, Yang Do Choi, Ju-Kon Kim
BACKGROUND: Plant stress responses and mechanisms determining tolerance are controlled by diverse sets of genes. Transcription factors (TFs) have been implicated in conferring drought tolerance under drought stress conditions, and the identification of their target genes can elucidate molecular regulatory networks that orchestrate tolerance mechanisms. RESULTS: We generated transgenic rice plants overexpressing the 4 rice TFs, OsNAC5, 6, 9, and 10, under the control of the root-specific RCc3 promoter...
January 12, 2018: BMC Genomics
https://www.readbyqxmd.com/read/29329290/morc2b-is-essential-for-meiotic-progression-and-fertility
#17
Baolu Shi, Jiangyang Xue, Jian Zhou, Seth D Kasowitz, Yuanwei Zhang, Guanxiang Liang, Yongjuan Guan, Qinghua Shi, Mingxi Liu, Jiahao Sha, Xiaoyan Huang, P Jeremy Wang
The microrchidia (MORC) family proteins are chromatin-remodelling factors and function in diverse biological processes such as DNA damage response and transposon silencing. Here, we report that mouse Morc2b encodes a functional germ cell-specific member of the MORC protein family. Morc2b arose specifically in the rodent lineage through retrotransposition of Morc2a during evolution. Inactivation of Morc2b leads to meiotic arrest and sterility in both sexes. Morc2b-deficient spermatocytes and oocytes exhibit failures in chromosomal synapsis, blockades in meiotic recombination, and increased apoptosis...
January 12, 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29328452/hif%C3%A2-1%C3%AE-%C3%A2-induced-upregulation-of-lncrna-uca1-promotes-cell-growth-in-osteosarcoma-by-inactivating-the-pten-akt-signaling-pathway
#18
Tengfei Li, Yang Xiao, Tunsheng Huang
Increasing evidence indicates that long non‑coding RNAs (lncRNAs) play an important role in multiple biological processes including cell growth, differentiation, proliferation and invasion. Urothelial carcinoma associated 1 (UCA1) is a highly conserved nuclear ncRNA and a key regulator of cell proliferation and apoptosis in several types of cancers. However, its role in osteosarcoma progression is not well known. In the present study, we aimed to determine the biological role of UCA1 in osteosarcoma progression...
January 3, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29327674/insoluble-microenvironment-facilitating-the-generation-and-maintenance-of-pluripotency
#19
Xiaofang Chen, Jiaqi Li, Yan Huang, Peng Liu, Yubo Fan
Induced pluripotent stem cells (iPSCs) hold enormous potential as a tool to generate cells for tissue engineering and regenerative medicine. Since the initial report of iPSCs in 2006, many different methods have been developed in order to enhance the safety and efficiency of this technology. Recent studies indicate that the extracellular signals can promote the production of iPSCs, and even replace the Yamanaka factors. Noticeably, abundant evidences suggest that the insoluble microenvironment, including the culture substrate and neighboring cells, directly regulates the expression of core pluripotency genes and the epigenetic modification of the chromatins, hence impact the reprogramming dynamics...
January 12, 2018: Tissue Engineering. Part B, Reviews
https://www.readbyqxmd.com/read/29326300/relationship-between-histone-modifications-and-transcription-factor-binding-is-protein-family-specific
#20
Beibei Xin, Remo Rohs
The very small fraction of putative binding sites (BSs) that are occupied by transcription factors (TFs) in vivo can be highly variable across different cell types. This observation has been partly attributed to changes in chromatin accessibility and histone modification (HM) patterns surrounding BSs. Previous studies focusing on BSs within DNA regulatory regions found correlations between HM patterns and TF binding specificities. However, a mechanistic understanding of TF-DNA binding specificity determinants is still not available...
January 11, 2018: Genome Research
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