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Epigenetic regulation of chromosome

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https://www.readbyqxmd.com/read/27909216/molecular-determinants-of-pathogenesis-and-clinical-phenotype-in-myeloproliferative-neoplasms
#1
Jacob Grinfeld, Jyoti Nangalia, Anthony R Green
The myeloproliferative neoplasms are a heterogeneous group of clonal disorders characterised by overproduction of mature cells in the peripheral blood, together with an increased risk of thrombosis and progression to acute myeloid leukemia. The majority of patients with Philadelphia-chromosome negative myeloproliferative neoplasms harbour somatic mutations in Janus kinase 2, leading to constitutive activation. Acquired mutations in calreticulin or myeloproliferative leukemia virus oncogene are found in a significant number of patients with essential thrombocythaemia or myelofibrosis, and mutations in numerous epigenetic regulators and spliceosome components are also seen...
December 1, 2016: Haematologica
https://www.readbyqxmd.com/read/27903646/whole-transcriptome-sequencing-identified-a-distinct-subtype-of-acute-lymphoblastic-leukemia-with-predominant-genomic-abnormalities-of-ep300-and-crebbp
#2
Maoxiang Qian, Hui Zhang, Shirley Kow-Yin Kham, Shuguang Liu, Chuang Jiang, Xujie Zhao, Yi Lu, Charnise Goodings, Ting-Nien Lin, Ranran Zhang, Takaya Moriyama, Zhaohong Yin, Zhenhua Li, Thuan Chong Quah, Hany Ariffin, Ah Moy Tan, Shuhong Shen, Deepa Bhojwani, Shaoyan Hu, Suning Chen, Huyong Zheng, Ching-Hon Pui, Allen Eng-Juh Yeoh, Jun J Yang
Chromosomal translocations are a genomic hallmark of many hematologic malignancies. Often as initiating events, these structural abnormalities result in fusion proteins involving transcription factors important for hematopoietic differentiation and/or signaling molecules regulating cell proliferation and cell cycle. In contrast, epigenetic regulator genes are more frequently targeted by somatic sequence mutations, possibly as secondary events to further potentiate leukemogenesis. Through comprehensive whole transcriptome sequencing of 231 children with acute lymphoblastic leukemia (ALL), we identified 58 putative functional and predominant fusion genes in 54...
November 30, 2016: Genome Research
https://www.readbyqxmd.com/read/27895219/primer-in-genetics-and-genomics-article-1-dna-genes-and-chromosomes
#3
Janice S Dorman, Mandy J Schmella, Susan W Wesmiller
Precision medicine refers to the practice of determining a patient's unique genetic, biomarker, and other characteristics for the purpose of improving his or her clinical outcomes. Not all patients with the same clinical diagnosis respond equally to identical treatment regimens. By examining patients at the molecular level, health-care providers will be better able to apply the most effective therapies that each individual requires. To understand precision medicine, nurses must have a solid understanding of genomics and proteomics...
November 28, 2016: Biological Research for Nursing
https://www.readbyqxmd.com/read/27889084/linking-telomere-regulation-to-stem-cell-pluripotency
#4
REVIEW
Lin Liu
Embryonic stem cells (ESCs), somatic cell nuclear transfer ESCs, and induced pluripotent stem cells (iPSCs) represent the most studied group of PSCs. Unlimited self-renewal without incurring chromosomal instability and pluripotency are essential for the potential use of PSCs in regenerative therapy. Telomere length maintenance is critical for the unlimited self-renewal, pluripotency, and chromosomal stability of PSCs. While telomerase has a primary role in telomere maintenance, alternative lengthening of telomere pathways involving recombination and epigenetic modifications are also required for telomere length regulation, notably in mouse PSCs...
November 23, 2016: Trends in Genetics: TIG
https://www.readbyqxmd.com/read/27879258/nucleophosmin-anaplastic-lymphoma-kinase-npm-alk-the-ultimate-oncogene-and-therapeutic-target
#5
Michael T Werner, Chen Zhao, Qian Zhang, Mariusz A Wasik
Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase physiologically expressed by fetal neural cells. However, aberrantly expressed ALK is involved in the pathogenesis of diverse malignancies including distinct types of lymphoma, lung carcinoma, and neuroblastoma. The aberrant ALK expression in non-neural cells results from chromosomal translocations that create novel fusion proteins. These protein hybrids are comprised of the proximal part of a partner gene including its promoter region and the distal part of ALK including coding sequence for the entire kinase domain...
November 22, 2016: Blood
https://www.readbyqxmd.com/read/27872008/the-genetic-basis-of-peyronie-disease-a-review
#6
REVIEW
Amin S Herati, Alexander W Pastuszak
INTRODUCTION: Peyronie disease (PD) is a progressive fibrotic disorder of the penile tunica albuginea that results in fibrotic penile plaques and can lead to penile deformity. Characterized by aberrant fibrosis resulting in part from the persistence of myofibroblasts and altered gene expression, the molecular factors underpinning PD and other related fibrotic diatheses are just being elucidated. A genetic link to PD was first identified three decades ago using pedigree analyses. However, the specific genetic factors that predispose patients to aberrant fibrosis remain unknown, and the relations between these fibrotic conditions and other heritable diseases, including malignancy, are uncharacterized...
January 2016: Sexual Medicine Reviews
https://www.readbyqxmd.com/read/27870402/genetic-and-epigenetic-factors-underlying-sex-differences-in-the-regulation-of-gene-expression-in-the-brain
#7
REVIEW
Vikram S Ratnu, Michael R Emami, Timothy W Bredy
There are inherent biological differences between males and females that contribute to sex differences in brain function and to many sex-specific illnesses and disorders. Traditionally, it has been thought that such differences are due largely to hormonal regulation; however, there are also genetic and epigenetic effects caused by the inheritance and unequal dosage of genes located on the X and Y chromosomes. Here we discuss the evidence in favor of a genetic and epigenetic basis for sexually dimorphic behavior, as a consequence of underlying differences in the regulation of genes that drive brain function...
January 2, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/27863966/activation-of-telomerase-by-hpvs
#8
REVIEW
Rachel A Katzenellenbogen
Telomerase extends the ends of linear chromosomes, and its expression leads to cellular immortalization. In HPV-associated cancers, telomerase is universally detected, and this occurs by activation of the catalytic subunit of telomerase, hTERT. The expression of hTERT is affected by both high-risk HPV E6 and E7. Seminal studies over the last two decades have identified the transcriptional, epigenetic, and post-transcriptional roles high-risk E6 and E7 have in telomerase regulation. This review will summarize these findings and highlight the importance of telomerase activation as an oncogenic pathway in HPV-associated cancer development and progression...
November 15, 2016: Virus Research
https://www.readbyqxmd.com/read/27857131/epigenetic-silencing-of-mir-137-induces-drug-resistance-and-chromosomal-instability-by-targeting-aurka-in-multiple-myeloma
#9
Y Qin, S Zhang, S Deng, G An, X Qin, F Li, Y Xu, M Hao, Y Yang, W Zhou, H Chang, L Qiu
Multiple myeloma (MM) is the second most prevalent hematologic malignancy. Aberrant microRNAs (miRNAs) expression has been shown to be involved in the pathogenesis of MM. In this study, we further demonstrated that miR-137 was significantly downregulated in MM and negatively correlated with clinical prognosis. Moreover, we described the epigenetic regulation of miR-137 and its association with progression free survival in MM patients. Furthermore, overexpression of miR-137 in MM cell line (miR-137OE) increased its sensitivity to bortezomib and eprirubicin in vitro...
November 18, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27845378/sex-specific-effects-of-testosterone-on-the-sexually-dimorphic-transcriptome-and-epigenome-of-embryonic-neural-stem-progenitor-cells
#10
Matthew S Bramble, Lara Roach, Allen Lipson, Neerja Vashist, Ascia Eskin, Tuck Ngun, Jason E Gosschalk, Steven Klein, Hayk Barseghyan, Valerie A Arboleda, Eric Vilain
The mechanisms by which sex differences in the mammalian brain arise are poorly understood, but are influenced by a combination of underlying genetic differences and gonadal hormone exposure. Using a mouse embryonic neural stem cell (eNSC) model to understand early events contributing to sexually dimorphic brain development, we identified novel interactions between chromosomal sex and hormonal exposure that are instrumental to early brain sex differences. RNA-sequencing identified 103 transcripts that were differentially expressed between XX and XY eNSCs at baseline (FDR = 0...
November 15, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27833942/random-positioning-of-nucleosomes-enhances-heritable-bistability
#11
Heli Tan, Tuoqi Liu, Jiajun Zhang, Tianshou Zhou
Chromosomal regions are often dynamically modified by histones, leading to the uncertainty of nucleosome positions. Experiments have provided evidence for this randomness, but it is unclear how it impacts epigenetic heritability. Here, by analyzing a mechanic model at the molecular level, which considers three representative types of nucleosomes (unmodified, methylated, and acetylated) and dynamic nucleosome modifications, we find that in contrast to the equidistance partition of nucleosomes, random partition can significantly enhance heritable bistability...
November 11, 2016: Molecular BioSystems
https://www.readbyqxmd.com/read/27824951/epigenetic-signatures-at-aqp3-and-socs3-engage-in-low-grade-inflammation-across-different-tissues
#12
Carola Marzi, Lesca M Holdt, Giovanni Fiorito, Pei-Chien Tsai, Anja Kretschmer, Simone Wahl, Simonetta Guarrera, Daniel Teupser, Tim D Spector, Licia Iacoviello, Carlotta Sacerdote, Konstantin Strauch, Serene Lee, Wolfgang E Thasler, Annette Peters, Barbara Thorand, Petra Wolf, Holger Prokisch, Rosario Tumino, Christian Gieger, Vittorio Krogh, Salvatore Panico, Jordana T Bell, Giuseppe Matullo, Melanie Waldenberger, Harald Grallert, Wolfgang Koenig
BACKGROUND: Elevated levels of C-reactive protein (CRP, determined by a high-sensitivity assay) indicate low-grade inflammation which is implicated in many age-related disorders. Epigenetic studies on CRP might discover molecular mechanisms underlying CRP regulation. We aimed to identify DNA methylation sites related to CRP concentrations in cells and tissues regulating low-grade inflammation. RESULTS: Genome-wide DNA methylation was measured in peripheral blood in 1,741 participants of the KORA F4 study using Illumina HumanMethylation450 BeadChip arrays...
2016: PloS One
https://www.readbyqxmd.com/read/27821526/split-hand-foot-malformation-genetics-supports-the-chromosome-7-copy-segregation-mechanism-for-human-limb-development
#13
REVIEW
Amar J S Klar
Genetic aberrations of several unlinked loci cause human congenital split hand/foot malformation (SHFM) development. Mutations of the DLX5 (distal-less) transcription factor-encoding gene in chromosome 7 cause SHFM through haploinsufficiency, but the vast majority of cases result from heterozygous chromosomal aberrations of the region without mutating the DLX5 gene. To resolve this paradox, we invoke a chromosomal epigenetic mechanism for limb development. It is composed of a monochromatid gene expression phenomenon that we discovered in two fission yeasts with the selective chromosome copy segregation phenomenon that we discovered in mouse cells...
December 19, 2016: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/27815388/loss-of-the-methyl-cpg-binding-protein-zbtb4-alters-mitotic-checkpoint-increases-aneuploidy-and-promotes-tumorigenesis
#14
Audrey Roussel-Gervais, Ikrame Naciri, Olivier Kirsh, Laetitia Kasprzyk, Guillaume Velasco, Giacomo Grillo, Pierre Dubus, Pierre-Antoine Defossez
Chromosome segregation during mitosis is monitored by the mitotic checkpoint and is dependent upon DNA methylation. ZBTB4 is a mammalian epigenetic regulator with high affinity for methylated CpGs that localizes at pericentromeric heterochromatin and is frequently downregulated in cancer. Here we report that decreased ZBTB4 expression correlates with high genome instability across many frequent human cancers. In human cell lines, ZBTB4 depletion was sufficient to increase the prevalence of micronuclei and binucleated cells in parallel with aberrant mitotic checkpoint gene expression, a weakened mitotic checkpoint, and an increased frequency of lagging chromosomes during mitosis...
November 4, 2016: Cancer Research
https://www.readbyqxmd.com/read/27814638/new-insights-on-the-role-of-dna-methylation-from-a-global-view
#15
Karin Meier, Félix Recillas-Targa
In mammals, DNA methylation is a crucial epigenetic modification with key functions during development. Cellular processes that are regulated by DNA methylation comprise X chromosome inactivation, gene imprinting, genomic stability and transcriptional regulation. Generally, the methylation status of the majority of target sites is reliably propagated during mitosis. However, advances in genome-wide DNA methylation analysis at base-resolution have discovered a substantial amount of differential DNA methylation between normal cells of different tissue-origin...
January 1, 2017: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/27810411/microbiome-driven-carcinogenesis-in-colorectal-cancer-models-and-mechanisms
#16
REVIEW
Xingmin Wang, Yonghong Yang, Mark M Huycke
Colorectal cancer (CRC) is a leading cause of cancer death and archetype for cancer as a genetic disease. However, the mechanisms for genetic change and their interactions with environmental risk factors have been difficult to unravel. New hypotheses, models, and methods are being used to investigate a complex web of risk factors that includes the intestinal microbiome. Recent research has clarified how the microbiome can generate genomic change in CRC. Several phenotypes among a small group of selected commensals have helped us better understand how mutations and chromosomal instability (CIN) are induced in CRC (e...
October 31, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27795737/expression-and-epigenomic-landscape-of-the-sex-chromosomes-in-mouse-post-meiotic-male-germ-cells
#17
Charlotte Moretti, Daniel Vaiman, Frederic Tores, Julie Cocquet
BACKGROUND: During meiosis, the X and Y chromosomes are transcriptionally silenced. The persistence of repressive chromatin marks on the sex chromatin after meiosis initially led to the assumption that XY gene silencing persists to some extent in spermatids. Considering the many reports of XY-linked genes expressed and needed in the post-meiotic phase of mouse spermatogenesis, it is still unclear whether or not the mouse sex chromatin is a repressive or permissive environment, after meiosis...
2016: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/27795542/genetic-and-epigenetic-aberrations-of-pediatric-leukemia-and-clinical-applications
#18
Junko Takita
Pediatric acute lymphoblastic leukemia (ALL) is the most common pediatric cancer. Although fusion genes generated by chromosomal rearrangements are the most frequent genetic alterations in pediatric ALL, fusions are insufficient for the development of this disease, and thus, cannot serve as therapeutic targets for ALL. Recently, integrated genetic analysis using next generation sequencing technology has revealed the genetic landscapes of pediatric ALL. These studies disclosed that in addition to fusion genes, aberrations of cell proliferation pathways and epigenetic regulations are also involved in the pathogenesis of pediatric ALL...
2016: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/27777940/epigenetic-regulation-of-human-dclk-1-gene-during-colon-carcinogenesis-clinical-and-mechanistic-implications
#19
COMMENT
Pomila Singh, Malaney O'Connell, Sarkar Shubhashish
Colorectal carcinogenesis is a multi-step process. While ~25% of colorectal cancers (CRCs) arise in patients with a family history (genetic predisposition), ~75% of CRCs are due to age-associated accumulation of epigenetic alterations which can result in the suppression of key tumor suppressor genes leading to mutations and activation of oncogenic pathways. Sporadic colon-carcinogenesis is facilitated by many molecular pathways of genomic instability which include chromosomal instability (CIN), micro-satellite instability (MSI) and CpG island methylator phenotype (CIMP), leading towards loss of homeostasis and onset of neoplastic transformation...
2016: Stem Cell Investigation
https://www.readbyqxmd.com/read/27770354/chromatin-conformation-capture-based-analysis-of-nuclear-architecture
#20
Stefan Grob, Ueli Grossniklaus
Nuclear organization and higher-order chromosome structure in interphase nuclei are thought to have important effects on fundamental biological processes, including chromosome condensation, replication, and transcription. Until recently, however, nuclear organization could only be analyzed microscopically. The development of chromatin conformation capture (3C)-based techniques now allows a detailed look at chromosomal architecture from the level of individual loci to the entire genome. Here we provide a robust Hi-C protocol, allowing the analysis of nuclear organization in nuclei from different wild-type and mutant plant tissues...
2017: Methods in Molecular Biology
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