A novel C-elegans zinc finger transcription factor, Isy-2, required for the cell type-specific expression of the Isy-6 microRNA

被引:38
作者
Johnston, RJ [1 ]
Hobert, O [1 ]
机构
[1] Columbia Univ, Med Ctr, Howard Hughes Med Inst, Ctr Neurobiol & Behav,Dept Biochem & Mol Biophys, New York, NY 10032 USA
来源
DEVELOPMENT | 2005年 / 132卷 / 24期
关键词
C; elegans; chemosensory neurons; laterality; fate determination; microRNA;
D O I
10.1242/dev.02163
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
The two Caenorhabditis elegans gustatory neurons, ASE left (ASEL) and ASE right (ASER) are morphologically bilaterally symmetric, yet left/right asymmetric in function and in the expression of specific chemosensory signaling molecules. The ASEL versus ASER cell-fate decision is controlled by a complex gene regulatory network composed of microRNAs (miRNAs) and transcription factors. Alterations in the activities of each of these regulatory factors cause a complete lateral cell-fate switch. Here, we describe lsy-2, a novel C2H2 zinc finger transcription factor that is required for the execution of the ASEL stable state. In lsy-2 null mutants, the ASEL neuron adopts the complete ASER gene expression profile, including both upstream regulatory and terminal effector genes. The normally left/right asymmetric ASE neurons are therefore 'symmetrized' in lsy-2 mutants. Cell-specific rescue experiments indicate that lsy-2 is required autonomously in ASEL for the activation of ASEL-specifying factors and the repression of ASER-specifying factors. Genetic epistasis experiments demonstrate that lsy-2 exerts its activity by regulating the transcription of the lsy-6 miRNA in the ASEL neuron, thereby making lsy-2 one of the few factors known to control the cell-type specificity of miRNA gene expression.
引用
收藏
页码:5451 / 5460
页数:10
相关论文
共 37 条
  • [1] Nuclear speckle-associated protein Pnn/DRS binds to the transcriptional corepressor CtBP and relieves CtBP-mediated repression of the E-cadherin gene
    Alpatov, R
    Munguba, GC
    Caton, P
    Joo, JH
    Shi, Y
    Shi, YJ
    Hunt, ME
    Sugrue, SP
    [J]. MOLECULAR AND CELLULAR BIOLOGY, 2004, 24 (23) : 10223 - 10235
  • [2] Altun-Gultekin Z, 2001, DEVELOPMENT, V128, P1951
  • [3] Subcellular localization and mechanisms of nucleocytoplasmic trafficking of steroid receptor coactivator-1
    Amazit, L
    Alj, Y
    Tyagi, RK
    Chauchereau, A
    Loosfelt, H
    Pichon, C
    Pantel, J
    Guinchard, EF
    Leclerc, P
    Milgrom, E
    Guiochon-Mantel, A
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (34) : 32195 - 32203
  • [4] HETEROCHRONIC MUTANTS OF THE NEMATODE CAENORHABDITIS-ELEGANS
    AMBROS, V
    HORVITZ, HR
    [J]. SCIENCE, 1984, 226 (4673) : 409 - 416
  • [5] The functions of animal microRNAs
    Ambros, V
    [J]. NATURE, 2004, 431 (7006) : 350 - 355
  • [6] Brenner S., 1974, GENETICS, V11, P1
  • [7] Chamberlin HM, 2000, DEVELOPMENT, V127, P713
  • [8] MicroRNAs act sequentially and asymmetrically to control chemosensory laterality in the nematode
    Chang, S
    Johnston, RJ
    Frokjær-Jensen, C
    Lockery, S
    Hobert, O
    [J]. NATURE, 2004, 430 (7001) : 785 - 789
  • [9] A transcriptional regulatory cascade that controls left/right asymmetry in chemosensory neurons of C-elegans
    Chang, S
    Johnston, RJ
    Hobert, O
    [J]. GENES & DEVELOPMENT, 2003, 17 (17) : 2123 - 2137
  • [10] SUMO modification of repression domains modulates function of nuclear receptor 5A1 (steroidogenic factor-1)
    Chen, WY
    Lee, WC
    Hsu, NC
    Huang, F
    Chung, BC
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (37) : 38730 - 38735