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https://www.readbyqxmd.com/read/29695247/impact-on-birth-weight-of-maternal-smoking-throughout-pregnancy-mediated-by-dna-methylation
#1
Stephanie H Witt, Josef Frank, Maria Gilles, Maren Lang, Jens Treutlein, Fabian Streit, Isabell A C Wolf, Verena Peus, Barbara Scharnholz, Tabea S Send, Stefanie Heilmann-Heimbach, Sugirthan Sivalingam, Helene Dukal, Jana Strohmaier, Marc Sütterlin, Janine Arloth, Manfred Laucht, Markus M Nöthen, Michael Deuschle, Marcella Rietschel
BACKGROUND: Cigarette smoking has severe adverse health consequences in adults and in the offspring of mothers who smoke during pregnancy. One of the most widely reported effects of smoking during pregnancy is reduced birth weight which is in turn associated with chronic disease in adulthood. Epigenome-wide association studies have revealed that smokers show a characteristic "smoking methylation pattern", and recent authors have proposed that DNA methylation mediates the impact of maternal smoking on birth weight...
April 25, 2018: BMC Genomics
https://www.readbyqxmd.com/read/29674496/gfi1-is-required-for-runx1-eto-positive-acute-myeloid-leukemia
#2
Anna E Marneth, Lacramioara Botezatu, Judith M Hönes, Jimmy C L Israël, Judith Schütte, Lothar Vassen, Robert F Lams, Saskia M Bergevoet, Laura Groothuis, Amit Mandoli, Joost H A Martens, Gerwin Huls, Joop H Jansen, Ulrich Dührsen, Tobias Berg, Tarik Möröy, Christian Wichmann, Mia-Chia Lo, Dong-Er Zhang, Bert A van der Reijden, Cyrus Khandanpour
No abstract text is available yet for this article.
April 19, 2018: Haematologica
https://www.readbyqxmd.com/read/29651020/gfi1-facilitates-efficient-dna-repair-by-regulating-prmt1-dependent-methylation-of-mre11-and-53bp1
#3
Charles Vadnais, Riyan Chen, Jennifer Fraszczak, Zhenbao Yu, Jonathan Boulais, Jordan Pinder, Daria Frank, Cyrus Khandanpour, Josée Hébert, Graham Dellaire, Jean-François Côté, Stéphane Richard, Alexandre Orthwein, Elliot Drobetsky, Tarik Möröy
GFI1 is a transcriptional regulator expressed in lymphoid cells, and an "oncorequisite" factor required for development and maintenance of T-lymphoid leukemia. GFI1 deletion causes hypersensitivity to ionizing radiation, for which the molecular mechanism remains unknown. Here, we demonstrate that GFI1 is required in T cells for the regulation of key DNA damage signaling and repair proteins. Specifically, GFI1 interacts with the arginine methyltransferase PRMT1 and its substrates MRE11 and 53BP1. We demonstrate that GFI1 enables PRMT1 to bind and methylate MRE11 and 53BP1, which is necessary for their function in the DNA damage response...
April 12, 2018: Nature Communications
https://www.readbyqxmd.com/read/29618728/association-between-dna-methylation-in-cord-blood-and-maternal-smoking-the-hokkaido-study-on-environment-and-children-s-health
#4
Kunio Miyake, Akio Kawaguchi, Ryu Miura, Sachiko Kobayashi, Nguyen Quoc Vuong Tran, Sumitaka Kobayashi, Chihiro Miyashita, Atsuko Araki, Takeo Kubota, Zentaro Yamagata, Reiko Kishi
Maternal smoking is reported to cause adverse effects on the health of the unborn child, the underlying mechanism for which is thought to involve alterations in DNA methylation. We examined the effects of maternal smoking on DNA methylation in cord blood, in 247 mother-infant pairs in the Sapporo cohort of the Hokkaido Study, using the Infinium HumanMethylation 450K BeadChip. We first identified differentially methylated CpG sites with a false discovery rate (FDR) of <0.05 and the magnitude of DNA methylation changes (|β| >0...
April 4, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29590629/enhancer-activation-by-pharmacologic-displacement-of-lsd1-from-gfi1-induces-differentiation-in-acute-myeloid-leukemia
#5
Alba Maiques-Diaz, Gary J Spencer, James T Lynch, Filippo Ciceri, Emma L Williams, Fabio M R Amaral, Daniel H Wiseman, William J Harris, Yaoyong Li, Sudhakar Sahoo, James R Hitchin, Daniel P Mould, Emma E Fairweather, Bohdan Waszkowycz, Allan M Jordan, Duncan L Smith, Tim C P Somervaille
Pharmacologic inhibition of LSD1 promotes blast cell differentiation in acute myeloid leukemia (AML) with MLL translocations. The assumption has been that differentiation is induced through blockade of LSD1's histone demethylase activity. However, we observed that rapid, extensive, drug-induced changes in transcription occurred without genome-wide accumulation of the histone modifications targeted for demethylation by LSD1 at sites of LSD1 binding and that a demethylase-defective mutant rescued LSD1 knockdown AML cells as efficiently as wild-type protein...
March 27, 2018: Cell Reports
https://www.readbyqxmd.com/read/29564582/novel-mutation-in-cecr1-leads-to-deficiency-of-ada2-with-associated-neutropenia
#6
Funda Erol Cipe, Cigdem Aydogmus, Nina K Serwas, Gonca Keskindemirci, Kaan Boztuğ
PURPOSE: Adenosine deaminase 2 (ADA2) have been reported to cause vasculitic diseases and immunodeficiency recently. Patients present with stroke episodes and rashes mimicking polyarteritis nodosa (PAN). We report a patient who has been followed up with severe neutropenia and found an unexpectedly revealed novel mutation in CECR1 affecting ADA2. METHODS: We reviewed medical records and clinical history of the patient. No mutations in other known neutropenia genes such as ELA, G6PC3, HAX1, AP3B1, LAMTOR2, VPS13B, VPS45, GFI1, JAGN1, or WAS could be detected...
March 21, 2018: Journal of Clinical Immunology
https://www.readbyqxmd.com/read/29327200/exocyst-complex-member-exoc5-is-required-for-survival-of-hair-cells-and-spiral-ganglion-neurons-and-maintenance-of-hearing
#7
Byeonghyeon Lee, Jeong-In Baek, Hyehyun Min, Seung-Hyun Bae, Kyeonghye Moon, Min-A Kim, Ye-Ri Kim, Ben Fogelgren, Joshua H Lipschutz, Kyu-Yup Lee, Jinwoong Bok, Un-Kyung Kim
The exocyst, an octameric protein complex consisting of Exoc1 through Exoc8, was first determined to regulate exocytosis by targeting vesicles to the plasma membrane in yeast to mice. In addition to this fundamental role, the exocyst complex has been implicated in other cellular processes. In this study, we investigated the role of the exocyst in cochlear development and hearing by targeting EXOC5, a central exocyst component. Deleting Exoc5 in the otic epithelium with widely used Cre lines resulted in early lethality...
January 11, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29302254/terminally-differentiating-eosinophils-express-neutrophil-primary-granule-proteins-as-well-as-eosinophil-specific-granule-proteins-in-a-temporal-manner
#8
Karam Kim, Sae Mi Hwang, Sung Min Kim, Sung Woo Park, Yunjae Jung, Il Yup Chung
Neutrophils and eosinophils, 2 prominent granulocytes, are commonly derived from myelocytic progenitors through successive stages in the bone marrow. Our previous genome-wide transcriptomic data unexpectedly showed that genes encoding a multitude of neutrophil primary granule proteins (NPGPs) were markedly downregulated during the end period of eosinophilic terminal differentiation when cord blood (CB) cluster of differentiation (CD) 34+ cells were induced to differentiate toward the eosinophil lineage during a 24-day culture period...
December 2017: Immune Network
https://www.readbyqxmd.com/read/29285874/early-cellular-interactions-and-immune-transcriptome-profiles-in-human-factor-viii-exposed-hemophilia-a-mice
#9
J D Lai, D Cartier, R B Hartholt, L L Swystun, A S van Velzen, J M M den Haan, C Hough, J Voorberg, D Lillicrap
Essentials Initial immune cell interactions leading to factor (F) VIII immunity are not well characterized. We assessed cellular interactions and expression profiles in hemophilia A mice. MARCO+, followed by SIGLEC1+ and SIGNR1+ macrophages co-localize most with human FVIII. The splenic transcriptome highlights potential therapeutic targets to prevent inhibitors. SUMMARY: Background Developing factor VIII (FVIII) inhibitory antibodies is the most serious complication in hemophilia A treatment, representing a significant health and economic burden...
March 2018: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/29282250/obesity-alters-the-long-term-fitness-of-the-hematopoietic-stem-cell-compartment-through-modulation-of-gfi1-expression
#10
Jung-Mi Lee, Vinothini Govindarajah, Bryan Goddard, Ashwini Hinge, David E Muench, Marie-Dominique Filippi, Bruce Aronow, Jose A Cancelas, Nathan Salomonis, H Leighton Grimes, Damien Reynaud
Obesity is a chronic organismal stress that disrupts multiple systemic and tissue-specific functions. In this study, we describe the impact of obesity on the activity of the hematopoietic stem cell (HSC) compartment. We show that obesity alters the composition of the HSC compartment and its activity in response to hematopoietic stress. The impact of obesity on HSC function is progressively acquired but persists after weight loss or transplantation into a normal environment. Mechanistically, we establish that the oxidative stress induced by obesity dysregulates the expression of the transcription factor Gfi1 and that increased Gfi1 expression is required for the abnormal HSC function induced by obesity...
February 5, 2018: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29232835/expression-profile-of-genes-regulating-steroid-biosynthesis-and-metabolism-in-human-ovarian-granulosa-cells-a-primary-culture-approach
#11
Wiesława Kranc, Maciej Brązert, Katarzyna Ożegowska, Mariusz J Nawrocki, Joanna Budna, Piotr Celichowski, Marta Dyszkiewicz-Konwińska, Maurycy Jankowski, Michal Jeseta, Leszek Pawelczyk, Małgorzata Bruska, Michał Nowicki, Maciej Zabel, Bartosz Kempisty
Because of the deep involvement of granulosa cells in the processes surrounding the cycles of menstruation and reproduction, there is a great need for a deeper understanding of the ways in which they function during the various stages of those cycles. One of the main ways in which the granulosa cells influence the numerous sex associated processes is hormonal interaction. Expression of steroid sex hormones influences a range of both primary and secondary sexual characteristics, as well as regulate the processes of oogenesis, folliculogenesis, ovulation, and pregnancy...
December 9, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29147018/enforced-gfi1-expression-impedes-human-and-murine-leukemic-cell-growth
#12
Judith M Hönes, Aniththa Thivakaran, Lacramioara Botezatu, Pradeep Patnana, Symone Vitoriano da Conceição Castro, Yahya S Al-Matary, Judith Schütte, Karen B I Fischer, Lothar Vassen, André Görgens, Ulrich Dührsen, Bernd Giebel, Cyrus Khandanpour
The differentiation of haematopoietic cells is regulated by a plethora of so-called transcription factors (TFs). Mutations in genes encoding TFs or graded reduction in their expression levels can induce the development of various malignant diseases such as acute myeloid leukaemia (AML). Growth Factor Independence 1 (GFI1) is a transcriptional repressor with key roles in haematopoiesis, including regulating self-renewal of haematopoietic stem cells (HSCs) as well as myeloid and lymphoid differentiation. Analysis of AML patients and different AML mouse models with reduced GFI1 gene expression levels revealed a direct link between low GFI1 protein level and accelerated AML development and inferior prognosis...
November 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29100035/the-role-of-human-chorionic-gonadotropin-in-regulation-of-na%C3%A3-ve-and-memory-t-cells-activity-in-vitro
#13
S A Zamorina, L S Litvinova, K A Yurova, O G Khaziakhmatova, V P Timganova, M S Bochkova, P V Khramtsov, M B Rayev
The role of human chorionic gonadotropin (hCG) in the regulation of molecular genetics factors determining the functional activity of human naïve and memory T cells in vitro was studied. It was found that hCG (10 and 100IU/ml) inhibited CD28 and CD25 expression on the naïve T cells (CD45RA+) and CD25 expression on the memory T cells (CD45R0+). hCG didn't affect the CD71 proliferation marker expression in total. Nevertheless, hCG reduced the percentage of proliferating memory T cells with simultaneous suppression of CD71 expression on proliferating CD45R0+cells...
January 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/28894287/prognostic-significance-of-high-gfi1-expression-in-aml-of-normal-karyotype-and-its-association-with-a-flt3-itd-signature
#14
Giacomo Volpe, David S Walton, David E Grainger, Carl Ward, Pierre Cauchy, Daniel Blakemore, Daniel J L Coleman, Peter N Cockerill, Paloma Garcia, Jon Frampton
Growth Factor Independence 1 (GFI1) is a transcriptional repressor that plays a critical role during both myeloid and lymphoid haematopoietic lineage commitment. Several studies have demonstrated the involvement of GFI1 in haematological malignancies and have suggested that low expression of GFI1 is a negative indicator of disease progression for both myelodysplastic syndromes (MDS) and acute myeloid leukaemia (AML). In this study, we have stratified AML patients into those defined as having a normal karyotype (CN-AML)...
September 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28820654/locus-specific-dna-methylation-in-the-placenta-is-associated-with-levels-of-pro-inflammatory-proteins-in-cord-blood-and-they-are-both-independently-affected-by-maternal-smoking-during-pregnancy
#15
Sanne D van Otterdijk, Alexandra M Binder, Karin B Michels
We investigated the impact of maternal smoking during pregnancy on placental DNA methylation and how this may mediate the association between maternal smoking and pro-inflammatory proteins in cord blood. The study population consisted of 27 individuals exposed to maternal smoking throughout pregnancy, 32 individuals exposed during a proportion of the pregnancy, and 61 unexposed individuals. Methylation of 11 regions within 6 genes in placenta tissue was assessed by pyrosequencing. Levels of 7 pro-inflammatory proteins in cord blood were assessed by electrochemiluminescence...
August 18, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28801480/gfi1-functions-in-transcriptional-control-and-cell-fate-determination-require-snag-domain-methylation-to-recruit-lsd1
#16
Matthew Velinder, Jason Singer, Diana Bareyan, Jessica Meznarich, Christopher M Tracy, James M Fulcher, David McClellan, Helena Lucente, Sarah Franklin, Sunil Sharma, Michael E Engel
No abstract text is available yet for this article.
August 11, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28662467/locus-specific-dna-methylation-changes-and-phenotypic-variability-in-children-with-attention-deficit-hyperactivity-disorder
#17
Sarojini M Sengupta, Alicia K Smith, Natalie Grizenko, Ridha Joober
Maternal smoking during pregnancy is the most commonly cited risk factor for ADHD. While the causal relation between this factor and ADHD is debated, several lines of evidence suggest that it modulates the severity of ADHD, particularly through higher association with conduct disorder (CD). We hypothesized that maternal smoking during pregnancy may be associated with differential methylation in selected genes in children with ADHD. DNA extracted from peripheral blood was used to examine methylation between 25 children exposed, and 22 children not exposed to maternal smoking during pregnancy...
June 20, 2017: Psychiatry Research
https://www.readbyqxmd.com/read/28574132/mirna-650-exerts-anti-leukemia-activity-by-inhibiting-cell-proliferation-through-gfi1-targeting
#18
Changyong Yuan, Liming Xu, Pengcheng Du, Jinling Pang
BACKGROUND: Acute myeloid leukemia (AML) is the most common malignancy of the bone marrow with a high mortality. Recent advances in high-throughput sequencing have led to the identification of various miRNAs implicated in the pathogenesis of AML. We found in this study that miR-650, a miRNA that was traditionally considered to participate in the onset of hepatocellular carcinoma, might play a significant role in AML development and progression. METHODS: qRT-PCR was used to detect the expression of miR-650 and Gfi1 in AML patients and healthy controls...
May 26, 2017: Tumori
https://www.readbyqxmd.com/read/28514438/conversion-of-adult-endothelium-to-immunocompetent-haematopoietic-stem-cells
#19
Raphael Lis, Charles C Karrasch, Michael G Poulos, Balvir Kunar, David Redmond, Jose G Barcia Duran, Chaitanya R Badwe, William Schachterle, Michael Ginsberg, Jenny Xiang, Arash Rafii Tabrizi, Koji Shido, Zev Rosenwaks, Olivier Elemento, Nancy A Speck, Jason M Butler, Joseph M Scandura, Shahin Rafii
Developmental pathways that orchestrate the fleeting transition of endothelial cells into haematopoietic stem cells remain undefined. Here we demonstrate a tractable approach for fully reprogramming adult mouse endothelial cells to haematopoietic stem cells (rEC-HSCs) through transient expression of the transcription-factor-encoding genes Fosb, Gfi1, Runx1, and Spi1 (collectively denoted hereafter as FGRS) and vascular-niche-derived angiocrine factors. The induction phase (days 0-8) of conversion is initiated by expression of FGRS in mature endothelial cells, which results in endogenous Runx1 expression...
May 25, 2017: Nature
https://www.readbyqxmd.com/read/28494218/maternal-cigarette-smoking-during-pregnancy-and-offspring-dna-methylation-in-midlife
#20
Parisa Tehranifar, Hui-Chen Wu, Jasmine A McDonald, Farzana Jasmine, Regina M Santella, Irina Gurvich, Julie D Flom, Mary Beth Terry
Maternal smoking in pregnancy (MSP) has been associated with DNA methylation in specific CpG sites (CpGs) in infants and children. We investigated whether MSP, independent of own personal active smoking, was associated with midlife DNA methylation in CpGs that were previously identified in studies of MSP-DNA methylation in children. We used data on MSP collected from pregnant mothers of 89 adult women born in 1959-1964 and measured DNA methylation in blood (granulocytes) collected in 2001-2007 (mean age: 43 years)...
2018: Epigenetics: Official Journal of the DNA Methylation Society
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