ATM Gene Mutations Result in Both Recessive and Dominant Expression Phenotypes of Genes and MicroRNAs Denis A. Smirnov, Vivian G. Cheung The American.

Slides:

Advertisements

Similar presentations

Functional Analysis of the Neurofibromatosis Type 2 Protein by Means of Disease- Causing Point Mutations Renee P. Stokowski, David R. Cox The American.

Advertisements

Inhibition of SOX17 by MicroRNA 141 and Methylation Activates the WNT Signaling Pathway in Esophageal Cancer Yan Jia, Yunsheng Yang, Qimin Zhan, Malcolm.

MLANA/MART1 and SILV/PMEL17/GP100 Are Transcriptionally Regulated by MITF in Melanocytes and Melanoma Jinyan Du, Arlo J. Miller, Hans R. Widlund, Martin.

MicroRNA-558 regulates the expression of cyclooxygenase-2 and IL-1β-induced catabolic effects in human articular chondrocytes S.J. Park, E.J. Cheon,

Volume 144, Issue 3, Pages e4 (March 2013)

Volume 16, Issue 5, Pages (August 2016)

Volume 107, Issue 7, Pages (December 2001)

MicroRNA-451 plays a role in murine embryo implantation through targeting Ankrd46, as implicated by a microarray-based analysis Zhengyu Li, M.D., Jia.

MiR-29 Regulates Type VII Collagen in Recessive Dystrophic Epidermolysis Bullosa Michael Vanden Oever, Daniel Muldoon, Wendy Mathews, Ron McElmurry, Jakub.

Circulating Exosomal miR-17-5p and miR-92a-3p Predict Pathologic Stage and Grade of Colorectal Cancer Fangfang Fu, Weiqin Jiang, Linfu Zhou, Zhi Chen

Crucial Roles of MZF1 and Sp1 in the Transcriptional Regulation of the Peptidylarginine Deiminase Type I Gene (PADI1) in Human Keratinocytes Sijun Dong,

MicroRNA-31 Promotes Skin Wound Healing by Enhancing Keratinocyte Proliferation and Migration Dongqing Li, X.I. Li, Aoxue Wang, Florian Meisgen, Andor.

MicroRNA-92a-3p regulates the expression of cartilage-specific genes by directly targeting histone deacetylase 2 in chondrogenesis and degradation G.

MicroRNA-92a-3p regulates the expression of cartilage-specific genes by directly targeting histone deacetylase 2 in chondrogenesis and degradation G.

MiR-29 Regulates Type VII Collagen in Recessive Dystrophic Epidermolysis Bullosa Michael Vanden Oever, Daniel Muldoon, Wendy Mathews, Ron McElmurry, Jakub.

MicroRNA221-3p modulates Ets-1 expression in synovial fibroblasts from patients with osteoarthritis of temporomandibular joint J. Xu, Y. Liu, M. Deng,

Volume 21, Issue 9, Pages (November 2017)

Psoriasis Skin Inflammation-Induced microRNA-26b Targets NCEH1 in Underlying Subcutaneous Adipose Tissue Louisa Cheung, Rachel M. Fisher, Natalia Kuzmina,

Inhibition of SOX17 by MicroRNA 141 and Methylation Activates the WNT Signaling Pathway in Esophageal Cancer Yan Jia, Yunsheng Yang, Qimin Zhan, Malcolm.

How MicroRNAs Modify Protein Production

Molecular Therapy - Nucleic Acids

MicroRNA-558 regulates the expression of cyclooxygenase-2 and IL-1β-induced catabolic effects in human articular chondrocytes S.J. Park, E.J. Cheon,

Substance P Enhances the Production of Interferon-induced Protein of 10 kDa by Human Keratinocytes in Synergy with Interferon-γ Naoko Kanda, Shinichi.

Volume 138, Issue 2, Pages (February 2010)

Yu Wang, M. D. , Ph. D. , Yang Lv, Ph. D. , Liyan Wang, M. D

Mutation of a Nuclear Respiratory Factor 2 Binding Site in the 5′ Untranslated Region of the ADSL Gene in Three Patients with Adenylosuccinate Lyase Deficiency

ATM Gene Mutations Result in Both Recessive and Dominant Expression Phenotypes of Genes and MicroRNAs Denis A. Smirnov, Vivian G. Cheung The American.

Human microRNA-155 on Chromosome 21 Differentially Interacts with Its Polymorphic Target in the AGTR1 3′ Untranslated Region: A Mechanism for Functional.

SOX10 Promotes Melanoma Cell Invasion by Regulating Melanoma Inhibitory Activity Saskia A. Graf, Christian Busch, Anja-Katrin Bosserhoff, Robert Besch,

M. Ushita, T. Saito, T. Ikeda, F. Yano, A. Higashikawa, N. Ogata, U

Rose-Anne Romano, Barbara Birkaya, Satrajit Sinha

SP1 was a downstream target of miR-150-3p

Volume 21, Issue 6, Pages (June 2013)

Volume 20, Issue 2, Pages (February 2018)

Volume 53, Issue 3, Pages (September 2010)

Mutual Repression by Bantam miRNA and Capicua Links the EGFR/MAPK and Hippo Pathways in Growth Control Héctor Herranz, Xin Hong, Stephen M. Cohen Current.

Volume 17, Issue 5, Pages (October 2016)

Edwards Allen, Zhixin Xie, Adam M. Gustafson, James C. Carrington Cell

Ovaries and Female Phenotype in a Girl with 46,XY Karyotype and Mutations in the CBX2 Gene Anna Biason-Lauber, Daniel Konrad, Monika Meyer, Carine deBeaufort,

MiR-125b, a MicroRNA Downregulated in Psoriasis, Modulates Keratinocyte Proliferation by Targeting FGFR2 Ning Xu, Petter Brodin, Tianling Wei, Florian.

Molecular Mechanisms Regulating the Defects in Fragile X Syndrome Neurons Derived from Human Pluripotent Stem Cells Tomer Halevy, Christian Czech, Nissim.

Hypermethylation of the CpG Island Near the G4C2 Repeat in ALS with a C9orf72 Expansion Zhengrui Xi, Lorne Zinman, Danielle Moreno, Jennifer Schymick,

Natalie R. Powers, John D. Eicher, Falk Butter, Yong Kong, Laura L

Molecular Therapy - Nucleic Acids

Aicardi-Goutières Syndrome Is Caused by IFIH1 Mutations

Splitting p63 The American Journal of Human Genetics

Molecular Therapy - Nucleic Acids

Inhibition of SOX17 by MicroRNA 141 and Methylation Activates the WNT Signaling Pathway in Esophageal Cancer Yan Jia, Yunsheng Yang, Qimin Zhan, Malcolm.

Promotion Effects of miR-375 on the Osteogenic Differentiation of Human Adipose- Derived Mesenchymal Stem Cells Si Chen, Yunfei Zheng, Shan Zhang, Lingfei.

Identification of the Transcriptional Targets of FOXP2, a Gene Linked to Speech and Language, in Developing Human Brain Elizabeth Spiteri, Genevieve.

Prediction of Plant MicroRNA Targets

Kun-Peng Zhu, Xiao-Long Ma, Chun-Lin Zhang Molecular Therapy

Volume 39, Issue 3, Pages (August 2010)

Improving the Assessment of the Outcome of Nonsynonymous SNVs with a Consensus Deleteriousness Score, Condel Abel González-Pérez, Nuria López-Bigas

miR-330-5p Targets Tyrosinase and Induces Depigmentation

Assessing the Functional Characteristics of Synonymous and Nonsynonymous Mutation Candidates by Use of Large DNA Constructs A.M. Eeds, D. Mortlock, R.

MELK Promotes Melanoma Growth by Stimulating the NF-κB Pathway

Negative Regulation of Tumor Suppressor p53 by MicroRNA miR-504

Volume 6, Issue 3, Pages (March 2016)

Mutations in CDON, Encoding a Hedgehog Receptor, Result in Holoprosencephaly and Defective Interactions with Other Hedgehog Receptors Gyu-Un Bae, Sabina.

Rational Design of Therapeutic siRNAs: Minimizing Off-targeting Potential to Improve the Safety of RNAi Therapy for Huntington's Disease Ryan L Boudreau,

Smith-Magenis Syndrome Results in Disruption of CLOCK Gene Transcription and Reveals an Integral Role for RAI1 in the Maintenance of Circadian Rhythmicity

Volume 21, Issue 6, Pages (November 2017)

The lncRNA PDIA3P Interacts with miR-185-5p to Modulate Oral Squamous Cell Carcinoma Progression by Targeting Cyclin D2 Cheng-Cao Sun, Ling Zhang, Guang.

The Expression of MicroRNA-598 Inhibits Ovarian Cancer Cell Proliferation and Metastasis by Targeting URI Feng Xing, Shuo Wang, Jianhong Zhou Molecular.

Lower levels of hsa-mir-15a, which decreases VEGFA, in the CD4+ T cells of pediatric patients with asthma Taiji Nakano, MD, Yuzaburo Inoue, MD, PhD,

Regulation of KSHV Lytic Switch Protein Expression by a Virus-Encoded MicroRNA: An Evolutionary Adaptation that Fine-Tunes Lytic Reactivation Priya Bellare,

Targeting DCLK1 by miRNA-137.

Molecular Therapy - Nucleic Acids

CREB1 binds at the proximal region of the TGFB2 promoter and induces its transcriptional activation. CREB1 binds at the proximal region of the TGFB2 promoter.

Presentation transcript:

ATM Gene Mutations Result in Both Recessive and Dominant Expression Phenotypes of Genes and MicroRNAs Denis A. Smirnov, Vivian G. Cheung The American Journal of Human Genetics Volume 83, Issue 2, Pages 243-253 (August 2008) DOI: 10.1016/j.ajhg.2008.07.003 Copyright © 2008 The American Society of Human Genetics Terms and Conditions

Figure 1 Gene-Expression Phenotypes of Noncarriers, AT Carriers, and AT Patients (A and B) An example of a gene, CDKN1A, that shows recessive pattern of expression (A) and a gene, FBXO5, that shows dominant pattern of expression (B) in response to radiation. (C and D) Twenty-two gene-expression phenotypes that show a recessive pattern of expression (C) and 29 gene-expression phenotypes that show a dominant pattern of expression (D). (E and F) Expression values were obtained with gene-expression microarrays and are presented as n-fold change relative to that of noncarriers at baseline. Two-way ANOVA was performed (p < 0.01, see Material and Methods); eight individuals per genotype were analyzed. Pathways identified with the Ingenuity program show that genes with recessive pattern (in purple) belong to the TP53-ATM pathway (E) and genes with dominant pattern (in light green) belong to the AKT-ATM pathway (F). The American Journal of Human Genetics 2008 83, 243-253DOI: (10.1016/j.ajhg.2008.07.003) Copyright © 2008 The American Society of Human Genetics Terms and Conditions

Figure 2 MicroRNA Phenotypes of Noncarriers, AT Carriers, and AT Patients Fifteen miRNA expression phenotypes that show a recessive pattern of expression (A), and seven miRNA phenotypes that show a dominant pattern of expression (B). Expression values were obtained with qRT-PCR and are presented as n-fold change relative to that of noncarriers at baseline. Two-way ANOVA was performed (p < 0.001, see Material and Methods); eight individuals per genotype were analyzed. miRNAs and their target genes that show recessive (C) and dominant (D) patterns of expression. The programs that predicted the miRNA and target-gene relationship are shown (PT = PicTar, TS = TargetScan, and MR = miRanda). Correlation coefficients for expression levels between the miRNAs and their targets are also shown. The American Journal of Human Genetics 2008 83, 243-253DOI: (10.1016/j.ajhg.2008.07.003) Copyright © 2008 The American Society of Human Genetics Terms and Conditions

Figure 3 TNFSF4 Is a Target Gene of MIRN125B (A) Protein level of TNFSF4 at baseline in AT carriers and patients as compared to noncarriers (n = 3 of each genotype). (B) The consensus binding sequence of MIRN125B located in the 3′UTR of TNFSF4 is shown. The sequence is highly conserved among species. (C) Luciferase-reporter assays in cells from noncarriers with wild-type binding sequence of MIRN125B in the 3′ UTR of TNFSF4 or mutant sequence where conserved binding site of MIRN125B was deleted (n = 3). (D) TNFSF4 mRNA levels in AT cells transfected with C.elegans miRNA or MIRN125B (n = 4). Error bars represent standard error of the mean. The American Journal of Human Genetics 2008 83, 243-253DOI: (10.1016/j.ajhg.2008.07.003) Copyright © 2008 The American Society of Human Genetics Terms and Conditions

Figure 4 CDX2 Regulates the Expression of MIRN125B (A) The expression level of CDX2 by qRT-PCR in AT carriers and patients and compared to noncarriers (n = 8 of each genotype). (B) Results of ChIP assay with CDX2 antibodies showing the binding of CDX2 to promoter of MIRN125B in AT carriers and patients as compared to noncarriers (n = 2 of each genotype). Error bars represent standard error of the mean. The American Journal of Human Genetics 2008 83, 243-253DOI: (10.1016/j.ajhg.2008.07.003) Copyright © 2008 The American Society of Human Genetics Terms and Conditions

Figure 5 Proposed Model of the Regulation of Expression Phenotypes ATM regulates transcription factors, such as CDX2, which regulate expression of microRNAs that in turn regulate expression level of genes, including TNFSF4. The American Journal of Human Genetics 2008 83, 243-253DOI: (10.1016/j.ajhg.2008.07.003) Copyright © 2008 The American Society of Human Genetics Terms and Conditions