DOCSLIB.ORG

How the Bach2 Basic Leucine Zipper Transcriptional Repressor Directs T Cell Differentiation and Function X X Martin J

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
How the Bach2 Basic Leucine Zipper Transcriptional Repressor Directs T Cell Differentiation and Function X X Martin J Th eJournal of Brief Reviews Immunology T Cell Fates Zipped Up: How the Bach2 Basic Leucine Zipper Transcriptional Repressor Directs T Cell Differentiation and Function x x Martin J. Richer,*,†,1 Mark L. Lang,‡, and Noah S. Butler‡, ,1 Recent data illustrate a key role for the transcriptional and T cells (4). In this review, we discuss our present un- regulator bric-a-brac, tramtrack, and broad complex derstanding of the role of Bach2 in regulating T cell devel- and cap’n’collar homology (Bach)2 in orchestrating opment and homeostasis, as well as the emerging role of Bach2 T cell differentiation and function. Although Bach2 in regulating the differentiation and function of effector and has a well-described role in B cell differentiation, emerg- memory T cells. The potential for Bach2 to regulate various ing data show that Bach2 is a prototypical member of a states of T cell activation, including quiescence and exhaustion, novel class of transcription factors that regulates tran- is also discussed. scriptional activity in T cells at super-enhancers, or regions of high transcriptional activity. Accumulating data dem- Bach2 basics onstrate specific roles for Bach2 in favoring regulatory Bach2 is a member of the Bach family of basic leucine zipper T cell generation, restraining effector T cell differentia- transcription factors (Fig. 1A). The Bach2 gene is located on tion, and potentiating memory T cell development. Ev- human chromosome 6, 6q15 (chromosome 4, 4A4 in mouse), idence suggests that Bach2 regulates various facets of and encodes a 741-aa protein whose functional domains are T cell function by repressing other key transcriptional highly conserved (.94%) in mice and humans (5, 6). Bach2 regulators such as B lymphocyte–induced maturation expression was originally described as being confined to the protein 1. In this review, we examine our present un- B cell lineage and to some neuronal cells that expressed a derstanding of the role of Bach2 in T cell function and neuron-specific splice variant (7). However, Bach2 expression highlight the growing evidence that this transcriptional was later identified in the T cell lineage where it was reported to bind the IL-2 promoter and was required for maintenance repressor functions as a key regulator involved in main- + tenance of T cell quiescence, T cell subset differentia- of IL-2 production by human cord blood CD4 T cells (8). tion, and memory T cell generation. The Journal of The basic leucine zipper transcription factors characteristi- cally form heterodimers through their leucine zippers with the Immunology, 2016, 197: 1009–1015. musculoaponeurotic fibrosarcoma (Maf) family of proteins yielding NF-E2 transcription factors (reviewed in Ref. 9). ignificant progress has been made in identifying and Bach2 forms heterodimers with small Maf proteins, including, delineating the effects of key transcriptional regulators MafF, MafG, and MafK, allowing binding to Maf recog- S that govern the diverse fates of lymphocytic effector nition elements (MAREs) with the consensus sequence subsets. One such regulator is the transcriptional repressor TGCTGA(G/C)TCA(T/C) (7) (Fig. 1B). Bach2 contains a bric-a-brac, tramtrack, and broad complex and cap’n’collar nuclear localization signal in its Zip domain and a nuclear homology (Bach)2. In addition to its well-defined role in export signal at its C terminus. Several factors regulate Bach2 B cell and plasma cell differentiation (recently reviewed in activity and localization (reviewed in Ref. 2), including PI3K Refs. 1–3), Bach2 is emerging as a functionally important signaling in B cells, which leads to phosphorylation of Ser512 regulator of other immune cell types, including macrophages and cytosolic accumulation. Oxidative stress inhibits the activity *Department of Microbiology and Immunology, McGill University, Montreal, Quebec of Allergy and Infectious Diseases Grant AI078993 and by funds from the Presbyterian H3A 2B4, Canada; †Microbiome and Disease Tolerance Centre, McGill University, Health Foundation of Oklahoma City. Montreal, Quebec H3A 2B4, Canada; ‡Department of Microbiology and Immunology, Address correspondence and reprint requests to Dr. Martin J. Richer or Dr. Noah S. Butler, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104; and x McGill University, Department of Microbiology and Immunology, 3775 University Graduate Program in Biosciences, University of Oklahoma Health Sciences Center, Street, Room 406, Montreal, QC H3A 2B4, Canada (M.J.R.) or University of Okla- Oklahoma City, OK 73104 homa Health Sciences Center, Department of Microbiology and Immunology, 940 1M.J.R. and N.S.B. contributed equally to this work. Stanton L. Young Boulevard, Oklahoma City, OK 73104 (N.S.B.). E-mail addresses: [email protected] (M.J.R.) or [email protected] (N.S.B.) ORCIDs: 0000-0002-5737-3217 (M.J.R.); 0000-0002-5137-0576 (M.L.L.); 0000- 0002-1429-0796 (N.S.B.). Abbreviations used in this article: Bach, bric-a-brac, tramtrack, and broad complex and cap’n’collar homology; Blimp-1, B lymphocyte–induced maturation protein 1; iTreg, Received for publication May 12, 2016. Accepted for publication June 8, 2016. peripherally induced regulatory T cell; Maf, musculoaponeurotic fibrosarcoma; MARE, M.J.R. is supported by funds from the Canada Foundation for Innovation (John R. Maf recognition element; miRNA, microRNA; PRDM1, PR domain zinc finger protein 1; Evans Leaders Fund) and by National Sciences and Engineering Research Council of ROR, retinoic acid–related orphan receptor; SE, super-enhancer; Treg, regulatory T cell; Canada Grant RGPIN-2016-04713. N.S.B. is supported by National Institutes of Tfh, T follicular helper. Health/National Institute of Allergy and Infectious Diseases Grant AI125446 and Na- tional Institutes of Health/National Institute of General Medical Sciences Grant Copyright Ó 2016 by The American Association of Immunologists, Inc. 0022-1767/16/$30.00 GM103447. M.L.L. is supported by National Institutes of Health/National Institute www.jimmunol.org/cgi/doi/10.4049/jimmunol.1600847 1010 BRIEF REVIEWS: REGULATION OF T CELLS BY Bach2 to susceptibility to different diseases, but they may have varying importance depending on the immune mechanisms driving pathology. Bach2 regulation of T cell development and homeostasis Originally described as a transcriptional regulator of B cells, it is now well appreciated that a/b T cells also express Bach2 FIGURE 1. Bach2 basics. (A) Schematic representation of Bach2 protein (Fig. 2A). Bach2-encoding mRNA has been detected in thymic structure. Broad complex–tamtrack–bric-a-brac (BTB) region, basic region, and peripheral T-lineage cells (21). Bach2 transcription grad- and leucine zipper are depicted. (B) DNA binding motif for Bach2. ually increases as T cells undergo differentiation and selection in the thymus, with more pronounced increases as T cells reach of the nuclear export signal and thus leads to nuclear the single-positive developmental stage (21). Expression is ad- accumulation. ditionally regulated upon thymic egress, at least in CD8 T cells, Bach2 function has been most extensively investigated in as Bach2 mRNA expression further increases in naive CD8 B cells where it is known to repress expression of B lymphocyte– T cells as they seed the periphery (21). The factors regulating induced maturation protein 1 (Blimp-1), also known as PR the expression of Bach2 in developing and mature T cells re- domain zinc finger protein 1 (PRDM1), by binding to the main poorly defined, but TCR crosslinking via Ag encounter MARE 59 of the prdm1 (Blimp-1) gene (10). Conditional may lead to a reduction in Bach2 expression. Consistent with ablation of Bach2 in the B cell lineage has revealed that Bach2 this, Ag-experienced effector and memory CD4 and CD8 downregulation is essential not only for Blimp-1 de-repression T cells recovered from the periphery express lower levels of and differentiation of B cells into plasma cells, but also for class Bach2 transcripts, compared with their naive counterparts (21). switch recombination leading to IgG1 secretion (11). However, As detailed below, cytokine signaling and other extrinsic factors the fates of B cells are not governed simply by Bach2 re- are likely important for modulating Bach2 expression or ac- pression of Blimp-1. Rather, a complex transcription factor tivity in T cells. Furthermore, the expression of Bach2 is likely network controls memory B cell and plasma cell differenti- to be posttranscriptionally regulated in lymphocytes, as CD4 ation and key molecular events concomitant with differentiation, T cells express lower amounts of Bach2 protein compared including class switch recombination, somatic hypermutation, with B cells, despite similar abundance of Bach2 transcripts and Ig secretion (1, 2). (21). Recent data also established that the epigenetic regulator MENIN promotes Bach2 expression in CD4 T cells via Bach2 in disease maintenance of histone acetylation at the bach2 locus. This The bach2 gene locus is susceptible to modifications that prevents T cell acquisition of a potentially damaging senescence- impact health. Aberrations in the long arm of chromosome 6 associated secretory phenotype, characterized in part by spon- are often associated with B cell malignancies. This includes a taneous proinflammatory cytokine production associated with Bach2–Bcl2LI fusion product detected in a lymphoma line loss of Bach2 expression (22), and further links Bach2 activity to (12). This resulted in enhanced expression of the antiapoptotic the maintenance of T cell homeostasis. Delineating the mech- protein Bcl2LI (also known as Bcl-xL). In another study, anisms that govern Bach2 transcription and posttranscriptional chromosomal rearrangements in an IgH-Myc–positive lym- regulation in T cells as they develop, mature, undergo ho- phoma resulted in fusion of exon 1 of IgHCd on 14q32 to meostatic proliferation, and respond to infection will be critical exon 2 of bach2 (13). The fusion transcript spanned the entire to further elucidate the biological role and function of Bach2 in coding region (exons 2–9) of bach2 and was highly expressed.
Load more

Recommended publications
  • B-Cell Malignancies in Microrna Eμ-Mir-17∼92 Transgenic Mice
    B-cell malignancies in microRNA Eμ-miR-17∼92 transgenic mice Sukhinder K. Sandhua, Matteo Fassana,b, Stefano Voliniaa,c, Francesca Lovata, Veronica Balattia, Yuri Pekarskya, and Carlo M. Crocea,1 aDepartment of Molecular Virology, Immunology and Medical Genetics, The Ohio State University Wexner Medical Center, Columbus, OH 43210; bARC-NET Research Centre, University of Verona, VR 37134, Verona, Italy; cDepartment of Morphology, Surgery and Experimental Medicine, University of Ferrara, FE 44121 Ferrara, Italy Contributed by Carlo M. Croce, September 22, 2013 (sent for review July 12, 2013) miR-17∼92 is a polycistronic microRNA (miR) cluster (consisting of cluster, but not of its paralogs, has shown that miR-17∼92 plays miR-17, miR-18a, miR-19a, miR-19b, miR-20a, and miR-92a) which an important role in B-cell development, and the KO mice die frequently is overexpressed in several solid and lymphoid malig- shortly after birth from lung hypoplasia and ventricular septal nancies. Loss- and gain-of-function studies have revealed the role defects (8). Further examination of the role of individual miRs in of miR-17∼92 in heart, lung, and B-cell development and in Myc- B-cell lymphomas showed that miR-19a and miR19b are required induced B-cell lymphomas, respectively. Recent studies indicate and sufficient for the proliferative activities of the cluster (9). that overexpression of this locus leads to lymphoproliferation, To understand better the role of the miR-17∼92 cluster in but no experimental proof that dysregulation of this cluster causes B-cell neoplastic progression, we generated miR-17∼92 B-cell– B-cell lymphomas or leukemias is available.
    [Show full text]
  • Coactivation of NF-Kb and Notch Signaling Is Sufficient to Induce B
    Regular Article LYMPHOID NEOPLASIA Coactivation of NF-kB and Notch signaling is sufficient to induce B-cell transformation and enables B-myeloid conversion Downloaded from https://ashpublications.org/blood/article-pdf/135/2/108/1550992/bloodbld2019001438.pdf by UNIV OF IOWA LIBRARIES user on 20 February 2020 Yan Xiu,1,* Qianze Dong,1,2,* Lin Fu,1,2 Aaron Bossler,1 Xiaobing Tang,1,2 Brendan Boyce,3 Nicholas Borcherding,1 Mariah Leidinger,1 Jose´ Luis Sardina,4,5 Hai-hui Xue,6 Qingchang Li,2 Andrew Feldman,7 Iannis Aifantis,8 Francesco Boccalatte,8 Lili Wang,9 Meiling Jin,9 Joseph Khoury,10 Wei Wang,10 Shimin Hu,10 Youzhong Yuan,11 Endi Wang,12 Ji Yuan,13 Siegfried Janz,14 John Colgan,15 Hasem Habelhah,1 Thomas Waldschmidt,1 Markus Muschen,¨ 9 Adam Bagg,16 Benjamin Darbro,17 and Chen Zhao1,18 1Department of Pathology, Carver College of Medicine, University of Iowa, Iowa City, IA; 2Department of Pathology, China Medical University, Shenyang, China; 3Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY; 4Gene Regulation, Stem Cells and Cancer Program, Centre for Genomic Regulation, Barcelona Institute of Science and Technology, Barcelona, Spain; 5Josep Carreras Leukaemia Research Institute, Campus ICO-Germans Trias i Pujol, Barcelona, Spain; 6Department of Microbiology and Immunology, Carver College of Medicine, University of Iowa, Iowa City, IA; 7Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Rochester, MN; 8Department of Pathology, NYU School of Medicine,
    [Show full text]
  • Supplementary Table S4. FGA Co-Expressed Gene List in LUAD
    Supplementary Table S4. FGA co-expressed gene list in LUAD tumors Symbol R Locus Description FGG 0.919 4q28 fibrinogen gamma chain FGL1 0.635 8p22 fibrinogen-like 1 SLC7A2 0.536 8p22 solute carrier family 7 (cationic amino acid transporter, y+ system), member 2 DUSP4 0.521 8p12-p11 dual specificity phosphatase 4 HAL 0.51 12q22-q24.1histidine ammonia-lyase PDE4D 0.499 5q12 phosphodiesterase 4D, cAMP-specific FURIN 0.497 15q26.1 furin (paired basic amino acid cleaving enzyme) CPS1 0.49 2q35 carbamoyl-phosphate synthase 1, mitochondrial TESC 0.478 12q24.22 tescalcin INHA 0.465 2q35 inhibin, alpha S100P 0.461 4p16 S100 calcium binding protein P VPS37A 0.447 8p22 vacuolar protein sorting 37 homolog A (S. cerevisiae) SLC16A14 0.447 2q36.3 solute carrier family 16, member 14 PPARGC1A 0.443 4p15.1 peroxisome proliferator-activated receptor gamma, coactivator 1 alpha SIK1 0.435 21q22.3 salt-inducible kinase 1 IRS2 0.434 13q34 insulin receptor substrate 2 RND1 0.433 12q12 Rho family GTPase 1 HGD 0.433 3q13.33 homogentisate 1,2-dioxygenase PTP4A1 0.432 6q12 protein tyrosine phosphatase type IVA, member 1 C8orf4 0.428 8p11.2 chromosome 8 open reading frame 4 DDC 0.427 7p12.2 dopa decarboxylase (aromatic L-amino acid decarboxylase) TACC2 0.427 10q26 transforming, acidic coiled-coil containing protein 2 MUC13 0.422 3q21.2 mucin 13, cell surface associated C5 0.412 9q33-q34 complement component 5 NR4A2 0.412 2q22-q23 nuclear receptor subfamily 4, group A, member 2 EYS 0.411 6q12 eyes shut homolog (Drosophila) GPX2 0.406 14q24.1 glutathione peroxidase
    [Show full text]
  • 1714 Gene Comprehensive Cancer Panel Enriched for Clinically Actionable Genes with Additional Biologically Relevant Genes 400-500X Average Coverage on Tumor
    xO GENE PANEL 1714 gene comprehensive cancer panel enriched for clinically actionable genes with additional biologically relevant genes 400-500x average coverage on tumor Genes A-C Genes D-F Genes G-I Genes J-L AATK ATAD2B BTG1 CDH7 CREM DACH1 EPHA1 FES G6PC3 HGF IL18RAP JADE1 LMO1 ABCA1 ATF1 BTG2 CDK1 CRHR1 DACH2 EPHA2 FEV G6PD HIF1A IL1R1 JAK1 LMO2 ABCB1 ATM BTG3 CDK10 CRK DAXX EPHA3 FGF1 GAB1 HIF1AN IL1R2 JAK2 LMO7 ABCB11 ATR BTK CDK11A CRKL DBH EPHA4 FGF10 GAB2 HIST1H1E IL1RAP JAK3 LMTK2 ABCB4 ATRX BTRC CDK11B CRLF2 DCC EPHA5 FGF11 GABPA HIST1H3B IL20RA JARID2 LMTK3 ABCC1 AURKA BUB1 CDK12 CRTC1 DCUN1D1 EPHA6 FGF12 GALNT12 HIST1H4E IL20RB JAZF1 LPHN2 ABCC2 AURKB BUB1B CDK13 CRTC2 DCUN1D2 EPHA7 FGF13 GATA1 HLA-A IL21R JMJD1C LPHN3 ABCG1 AURKC BUB3 CDK14 CRTC3 DDB2 EPHA8 FGF14 GATA2 HLA-B IL22RA1 JMJD4 LPP ABCG2 AXIN1 C11orf30 CDK15 CSF1 DDIT3 EPHB1 FGF16 GATA3 HLF IL22RA2 JMJD6 LRP1B ABI1 AXIN2 CACNA1C CDK16 CSF1R DDR1 EPHB2 FGF17 GATA5 HLTF IL23R JMJD7 LRP5 ABL1 AXL CACNA1S CDK17 CSF2RA DDR2 EPHB3 FGF18 GATA6 HMGA1 IL2RA JMJD8 LRP6 ABL2 B2M CACNB2 CDK18 CSF2RB DDX3X EPHB4 FGF19 GDNF HMGA2 IL2RB JUN LRRK2 ACE BABAM1 CADM2 CDK19 CSF3R DDX5 EPHB6 FGF2 GFI1 HMGCR IL2RG JUNB LSM1 ACSL6 BACH1 CALR CDK2 CSK DDX6 EPOR FGF20 GFI1B HNF1A IL3 JUND LTK ACTA2 BACH2 CAMTA1 CDK20 CSNK1D DEK ERBB2 FGF21 GFRA4 HNF1B IL3RA JUP LYL1 ACTC1 BAG4 CAPRIN2 CDK3 CSNK1E DHFR ERBB3 FGF22 GGCX HNRNPA3 IL4R KAT2A LYN ACVR1 BAI3 CARD10 CDK4 CTCF DHH ERBB4 FGF23 GHR HOXA10 IL5RA KAT2B LZTR1 ACVR1B BAP1 CARD11 CDK5 CTCFL DIAPH1 ERCC1 FGF3 GID4 HOXA11 IL6R KAT5 ACVR2A
    [Show full text]
  • Next Generation Exome Sequencing of Paediatric Inflammatory Bowel Disease Patients Identifies Rare and Novel Variants in Candida
    Gut Online First, published on April 28, 2012 as 10.1136/gutjnl-2011-301833 Inflammatory bowel disease ORIGINAL ARTICLE Gut: first published as 10.1136/gutjnl-2011-301833 on 28 April 2012. Downloaded from Next generation exome sequencing of paediatric inflammatory bowel disease patients identifies rare and novel variants in candidate genes Katja Christodoulou,1 Anthony E Wiskin,2 Jane Gibson,1 William Tapper,1 Claire Willis,2 Nadeem A Afzal,3 Rosanna Upstill-Goddard,1 John W Holloway,4 Michael A Simpson,5 R Mark Beattie,3 Andrew Collins,1 Sarah Ennis1 < Additional materials are ABSTRACT published online only. To view Background Multiple genes have been implicated by Significance of this study these files please visit the association studies in altering inflammatory bowel journal online (http://gut.bmj. com/content/early/recent). disease (IBD) predisposition. Paediatric patients often What is already known on this subject? manifest more extensive disease and a particularly < For numbered affiliations see Genome-wide association studies have impli- end of article. severe disease course. It is likely that genetic cated numerous candidate genes for inflamma- predisposition plays a more substantial role in this group. tory bowel disease (IBD), but evidence of Correspondence to Objective To identify the spectrum of rare and novel causality for specific variants is largely absent. Dr Sarah Ennis, Genetic variation in known IBD susceptibility genes using exome Furthermore, by design, genome-wide associa- Epidemiology and Genomic sequencing analysis in eight individual cases of childhood Informatics Group, Human tion studies are limited to the study of Genetics, Faculty of Medicine, onset severe disease.
    [Show full text]
  • Effects of Targeting the Transcription Factors Ikaros and Aiolos on B Cell Activation and Differentiation in Systemic Lupus Erythematosus
    Immunology and inflammation Lupus Sci Med: first published as 10.1136/lupus-2020-000445 on 16 March 2021. Downloaded from Effects of targeting the transcription factors Ikaros and Aiolos on B cell activation and differentiation in systemic lupus erythematosus Felice Rivellese ,1 Sotiria Manou- Stathopoulou,1 Daniele Mauro,1 Katriona Goldmann,1 Debasish Pyne,2 Ravindra Rajakariar,3 Patrick Gordon,4 Peter Schafer,5 Michele Bombardieri,1 Costantino Pitzalis,1 Myles J Lewis 1 To cite: Rivellese F, ABSTRACT Manou- Stathopoulou S, Objective To evaluate the effects of targeting Ikaros and Key messages Mauro D, et al. Effects of Aiolos by cereblon modulator iberdomide on the activation What is already known about this subject? targeting the transcription and differentiation of B- cells from patients with systemic factors Ikaros and Aiolos The transcription factors Ikaros and Aiolos, which lupus erythematosus (SLE). ► on B cell activation and are critical for B cell differentiation, are implicated in Methods CD19+ B- cells isolated from the peripheral differentiation in systemic systemic lupus erythematosus (SLE) pathogenesis. blood of patients with SLE (n=41) were cultured with lupus erythematosus. Targeting Ikaros and Aiolos using the cereblon mod- TLR7 ligand resiquimod ±IFNα together with iberdomide ► Lupus Science & Medicine ulator iberdomide has been proposed as a promising 2021;8:e000445. doi:10.1136/ or control from day 0 (n=16). Additionally, in vitro B- cell therapeutic agent. lupus-2020-000445 differentiation was induced by stimulation with IL-2/IL-10/ IL-15/CD40L/resiquimod with iberdomide or control, given What does this study add? at day 0 or at day 4.
    [Show full text]
  • Specification of the Hair Follicle Niche Occurs Prior to Its Formation and Is Progenitor Dependent
    bioRxiv preprint doi: https://doi.org/10.1101/414839; this version posted September 12, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Mok, Saxena, Heitman et al., 2018 Fate Before Function: Specification of the Hair Follicle Niche Occurs Prior to its Formation and Is Progenitor Dependent Ka-Wai Mok,1,2,9 Nivedita Saxena,1,2,3,9 Nicholas Heitman,1,2,3,9 Laura Grisanti,1,2 Devika Srivastava,1,2 Mauro Muraro,4 Tina Jacob,5 Rachel Sennett,1,2 Zichen Wang,6 Yutao Su,7 Lu M. Yang,7 Avi Ma’ayan,6 David M. Ornitz7, Maria Kasper,5 and Michael Rendl1,2,3,8,10,* 1Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, Atran Building AB7-10C, Box 1020; 1428 Madison Ave, New York, NY 10029, USA 2Department of Cell, Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, Atran Building AB7-10C, Box 1020; 1428 Madison Ave, New York, NY 10029, USA 3Graduate School of Biomedical Sciences; Icahn School of Medicine at Mount Sinai, Atran Building AB7-10C, Box 1020; 1428 Madison Ave, New York, NY 10029, USA 4Oncode Institute, Hubrecht Institute–KNAW (Royal Netherlands Academy of Arts and Sciences) and University Medical Center Utrecht, 3584 CT Utrecht, the Netherlands 5Department of Biosciences and Nutrition and Center for Innovative Medicine, Karolinska Institutet. 141 83 Huddinge, Sweden 6Department of Pharmacological Sciences, Mount Sinai Center for Bioinformatics, BD2K-LINCS Data Coordination and Integration Center, Knowledge Management Center for Illuminating the Druggable Genome (KMC-IDG), Icahn School of Medicine at Mount Sinai, One Gustave L.
    [Show full text]
  • Analysis of Estrogen-Regulated Genes in Mouse Uterus Using Cdna Microarray and Laser Capture Microdissection
    157 Analysis of estrogen-regulated genes in mouse uterus using cDNA microarray and laser capture microdissection Seok Ho Hong1,2, Hee Young Nah2, Ji Yoon Lee2, Myung Chan Gye1, Chung Hoon Kim2 and Moon Kyoo Kim1 1Department of Life Science, College of Natural Sciences, Hanyang University, Seoul 133-791, Korea 2Department of Obstetrics and Gynecology, College of Medicine, Ulsan University, Asan Medical Center, Seoul 138-746, Korea (Requests for offprints should be addressed toMKKim;Email: [email protected]) Abstract The steroid hormone, estrogen, plays an important role in protein 2, integral membrane protein 2B and chemokine various physiological events which are mediated via its ligand 12. The expression patterns of several selected genes nuclear estrogen receptors, ER and ER. However, the identified by the microarray analysis were confirmed by molecular mechanisms that are regulated by estrogen in RT-PCR. In addition, laser capture microdissection the uterus remain largely unknown. To identify genes that (LCM) was conducted to determine the expression of are regulated by estrogen, the ovariectomized mouse selected genes in specific uterine cell types. Analysis of uterus was exposed to 17-estradiol (E2) for 6 h and 12 h, early and late responsive genes using LCM and cDNA and the data were analyzed by cDNA microarray. The microarray not only suggests direct and indirect effects of present study confirms previous findings and identifies E2 on uterine physiological events, but also demonstrates several genes with expressions not previously known to be differential regulation of E2 in specific uterine cell types. influenced by estrogen. These genes include small proline- These results provide a basic background on global gene rich protein 2A, receptor-activity-modifying protein 3, alterations or genetic pathways in the uterus during the inhibitor of DNA binding-1, eukaryotic translation initia- estrous cycle and the implantation period.
    [Show full text]
  • Xo PANEL DNA GENE LIST
    xO PANEL DNA GENE LIST ~1700 gene comprehensive cancer panel enriched for clinically actionable genes with additional biologically relevant genes (at 400 -500x average coverage on tumor) Genes A-C Genes D-F Genes G-I Genes J-L AATK ATAD2B BTG1 CDH7 CREM DACH1 EPHA1 FES G6PC3 HGF IL18RAP JADE1 LMO1 ABCA1 ATF1 BTG2 CDK1 CRHR1 DACH2 EPHA2 FEV G6PD HIF1A IL1R1 JAK1 LMO2 ABCB1 ATM BTG3 CDK10 CRK DAXX EPHA3 FGF1 GAB1 HIF1AN IL1R2 JAK2 LMO7 ABCB11 ATR BTK CDK11A CRKL DBH EPHA4 FGF10 GAB2 HIST1H1E IL1RAP JAK3 LMTK2 ABCB4 ATRX BTRC CDK11B CRLF2 DCC EPHA5 FGF11 GABPA HIST1H3B IL20RA JARID2 LMTK3 ABCC1 AURKA BUB1 CDK12 CRTC1 DCUN1D1 EPHA6 FGF12 GALNT12 HIST1H4E IL20RB JAZF1 LPHN2 ABCC2 AURKB BUB1B CDK13 CRTC2 DCUN1D2 EPHA7 FGF13 GATA1 HLA-A IL21R JMJD1C LPHN3 ABCG1 AURKC BUB3 CDK14 CRTC3 DDB2 EPHA8 FGF14 GATA2 HLA-B IL22RA1 JMJD4 LPP ABCG2 AXIN1 C11orf30 CDK15 CSF1 DDIT3 EPHB1 FGF16 GATA3 HLF IL22RA2 JMJD6 LRP1B ABI1 AXIN2 CACNA1C CDK16 CSF1R DDR1 EPHB2 FGF17 GATA5 HLTF IL23R JMJD7 LRP5 ABL1 AXL CACNA1S CDK17 CSF2RA DDR2 EPHB3 FGF18 GATA6 HMGA1 IL2RA JMJD8 LRP6 ABL2 B2M CACNB2 CDK18 CSF2RB DDX3X EPHB4 FGF19 GDNF HMGA2 IL2RB JUN LRRK2 ACE BABAM1 CADM2 CDK19 CSF3R DDX5 EPHB6 FGF2 GFI1 HMGCR IL2RG JUNB LSM1 ACSL6 BACH1 CALR CDK2 CSK DDX6 EPOR FGF20 GFI1B HNF1A IL3 JUND LTK ACTA2 BACH2 CAMTA1 CDK20 CSNK1D DEK ERBB2 FGF21 GFRA4 HNF1B IL3RA JUP LYL1 ACTC1 BAG4 CAPRIN2 CDK3 CSNK1E DHFR ERBB3 FGF22 GGCX HNRNPA3 IL4R KAT2A LYN ACVR1 BAI3 CARD10 CDK4 CTCF DHH ERBB4 FGF23 GHR HOXA10 IL5RA KAT2B LZTR1 ACVR1B BAP1 CARD11 CDK5 CTCFL DIAPH1 ERCC1 FGF3 GID4 HOXA11
    [Show full text]
  • A Novel Risk Score System of Immune Genes Associated with Prognosis In
    Zhou et al. Cancer Cell Int (2020) 20:240 https://doi.org/10.1186/s12935-020-01317-5 Cancer Cell International PRIMARY RESEARCH Open Access A novel risk score system of immune genes associated with prognosis in endometrial cancer Hongyu Zhou1,3† , Chufan Zhang2,3† , Haoran Li3,4† , Lihua Chen3,4 and Xi Cheng1,3* Abstract Background: Endometrial cancer was the commonest gynecological malignancy in developed countries. Despite striking advances in multimodality management, however, for patients in advanced stage, targeted therapy still remained a challenge. Our study aimed to investigate new biomarkers for endometrial cancer and establish a novel risk score system of immune genes in endometrial cancer. Methods: The clinicopathological characteristics and gene expression data were downloaded from The Cancer Genome Atlas (TCGA) database. Diferentially expressed genes (DEGs) of immune genes between tumors and normal tissues were identifed. Protein–protein interaction (PPI) network of immune genes and transcriptional factors was integrated and visualized in Cytoscape. Univariate and multivariate analysis were employed for key genes to establish a new risk score system. Receiver operating characteristic (ROC) curve and survival analysis were performed to inves- tigate the prognostic value of the model. Association between clinical characteristics and the model was analyzed by logistic regression. For validation, we identifed 34 patients with endometrial cancer from Fudan University Shanghai Cancer Center (FUSCC). We detected 14-genes mRNA expression and calculated the risk scores of each patients and we performed survival analysis between the high-risk group and the low-risk group. Results: 23 normal tissues and 552 tumor tissues were obtained from TCGA database.
    [Show full text]
  • Interplay Between Cofactors and Transcription Factors in Hematopoiesis and Hematological Malignancies
    Signal Transduction and Targeted Therapy www.nature.com/sigtrans REVIEW ARTICLE OPEN Interplay between cofactors and transcription factors in hematopoiesis and hematological malignancies Zi Wang 1,2, Pan Wang2, Yanan Li2, Hongling Peng1, Yu Zhu2, Narla Mohandas3 and Jing Liu2 Hematopoiesis requires finely tuned regulation of gene expression at each stage of development. The regulation of gene transcription involves not only individual transcription factors (TFs) but also transcription complexes (TCs) composed of transcription factor(s) and multisubunit cofactors. In their normal compositions, TCs orchestrate lineage-specific patterns of gene expression and ensure the production of the correct proportions of individual cell lineages during hematopoiesis. The integration of posttranslational and conformational modifications in the chromatin landscape, nucleosomes, histones and interacting components via the cofactor–TF interplay is critical to optimal TF activity. Mutations or translocations of cofactor genes are expected to alter cofactor–TF interactions, which may be causative for the pathogenesis of various hematologic disorders. Blocking TF oncogenic activity in hematologic disorders through targeting cofactors in aberrant complexes has been an exciting therapeutic strategy. In this review, we summarize the current knowledge regarding the models and functions of cofactor–TF interplay in physiological hematopoiesis and highlight their implications in the etiology of hematological malignancies. This review presents a deep insight into the physiological and pathological implications of transcription machinery in the blood system. Signal Transduction and Targeted Therapy (2021) ;6:24 https://doi.org/10.1038/s41392-020-00422-1 1234567890();,: INTRODUCTION by their ATPase subunits into four major families, including the Hematopoiesisisacomplexhierarchicaldifferentiationprocessthat SWI/SNF, ISWI, Mi-2/NuRD, and INO80/SWR1 families.
    [Show full text]
  • Transcriptional Control of Regulatory T Cells in Cancer: Toward Therapeutic Targeting?
    cancers Review Transcriptional Control of Regulatory T Cells in Cancer: Toward Therapeutic Targeting? Pierre Stéphan y , Raphaëlle Lautraite y, Allison Voisin and Yenkel Grinberg-Bleyer * Cancer Research Center of Lyon, UMR INSERM 1052, CNRS 5286, Université Claude Bernard Lyon 1, Centre Léon Bérard, 69008 Lyon, France; [email protected] (P.S.); [email protected] (R.L.); [email protected] (A.V.) * Correspondence: [email protected]; Tel.: +33-(0)-469-856-248 These authors contributed equally to this paper. y Received: 9 October 2020; Accepted: 28 October 2020; Published: 30 October 2020 Simple Summary: Cancer outcomes are often indexed to the quality of the immune response to the tumor. Among immune cells, Foxp3+ regulatory T cells (Treg cells) are potent inhibitors of cancer immunity, and their presence within solid tumors is generally associated with a poor prognosis. Thus, understanding how Treg cell identity is controlled, is of utmost importance for the development of novel anti-cancer therapies. In this review, we summarize the current knowledge on the different intracellular pathways involved in the programming of Treg cell homeostasis and functions in cancer. We also highlight the therapeutic approaches aiming at targeting these regulators to enhance anti-tumor immunity. Abstract: Extensive research in the past decades has highlighted the tight link between immunity and cancer, leading to the development of immunotherapies that have revolutionized cancer care. However, only a fraction of patients display durable responses to these treatments, and a deeper understanding of the cellular and mechanisms orchestrating immune responses to tumors is mandatory for the discovery of novel therapeutic targets.
    [Show full text]