© The Rockefeller University Press,
0021-9525/1997//1343 $5.00
The Journal of Cell Biology, Volume 138, Number 6,
, 1997 1343-1354
Tissue-specific Expression of the L1 Cell Adhesion Molecule Is Modulated by the Neural Restrictive Silencer Element
Pekka Kallunki,
Gerald M. Edelman, and
Frederick S. Jones
Department of Neurobiology, The Scripps Research Institute and The Skaggs Institute for Chemical Biology, La Jolla, California 92037
The cell adhesion molecule L1 mediates neurite outgrowth and fasciculation during embryogenesis and mutations in its gene have been linked to a number of human congenital syndromes. To identify DNA sequences that restrict expression of L1 to the nervous system, we isolated a previously unidentified segment of the mouse L1 gene containing the promoter, the first exon, and the first intron and examined its activity in vitro and in vivo. We found that a neural restrictive silencer element (NRSE) within the second intron prevented expression of L1 gene constructs in nonneural cells. For optimal silencing of L1 gene expression by the NRSE-binding factor RE-1–silencing transcription factor (REST)/NRSF, both the NRSE and sequences in the first intron were required. In transgenic mice, an L1lacZ gene construct with the NRSE generated a neurally restricted expression pattern consistent with the known pattern of L1 expression in postmitotic neurons and peripheral glia. In contrast, a similar construct lacking the NRSE produced precocious expression in the peripheral nervous system and ectopic expression in mesenchymal derivatives of the neural crest and in mesodermal and ectodermal cells. These experiments show that the NRSE and REST/NRSF are important components in restricting L1 expression to the embryonic nervous system.
Abbreviations used in this paper: BMP, bone morphogenetic protein; CAM, cell adhesion molecule; CBP, CCAAT-binding protein; CNS and PNS, central and peripheral nervous system; E, embryonic day; HA, hemagglutinin; N-CAM, neural cell adhesion molecule; NF-1, nuclear factor-1; Ng-CAM, neuron-glia cell adhesion molecule; NRSE, neural restrictive silencer element; NRSF, neural restrictive silencer factor; RACE, rapid amplification of cDNA ends; REST, RE-1–silencing transcription factor; RLU, raw light units.
Address all correspondence to Frederick S. Jones, Department of Neurobiology, The Scripps Research Institute, 10550 North Torrey Pines Rd., La Jolla, CA 92037. Tel.: (619) 784-2600. Fax: (619) 784-2646. e-mail: fjones{at}scripps.edu

CiteULike
Complore
Connotea
Del.icio.us
Digg
Facebook
Reddit
Technorati
Twitter What's this?
This article has been cited by other articles:
-
HEUBNER, M., WIMBERGER, P., KASIMIR-BAUER, S., OTTERBACH, F., KIMMIG, R., SIFFERT, W.
(2009). The AA Genotype of a L1C G842A Polymorphism Is Associated with an Increased Risk for Ovarian Cancer. Anticancer Res
29: 3449-3452
[Abstract]
[Full Text]
-
Ding, N., Tomomori-Sato, C., Sato, S., Conaway, R. C., Conaway, J. W., Boyer, T. G.
(2009). MED19 and MED26 Are Synergistic Functional Targets of the RE1 Silencing Transcription Factor in Epigenetic Silencing of Neuronal Gene Expression. J. Biol. Chem.
284: 2648-2656
[Abstract]
[Full Text]
-
Ooi, L., Belyaev, N. D., Miyake, K., Wood, I. C., Buckley, N. J.
(2006). BRG1 Chromatin Remodeling Activity Is Required for Efficient Chromatin Binding by Repressor Element 1-silencing Transcription Factor (REST) and Facilitates REST-mediated Repression. J. Biol. Chem.
281: 38974-38980
[Abstract]
[Full Text]
-
Conaco, C., Otto, S., Han, J.-J., Mandel, G.
(2006). Reciprocal actions of REST and a microRNA promote neuronal identity. Proc. Natl. Acad. Sci. USA
103: 2422-2427
[Abstract]
[Full Text]
-
Gavert, N., Conacci-Sorrell, M., Gast, D., Schneider, A., Altevogt, P., Brabletz, T., Ben-Ze'ev, A.
(2005). L1, a novel target of {beta}-catenin signaling, transforms cells and is expressed at the invasive front of colon cancers. JCB
168: 633-642
[Abstract]
[Full Text]
-
Kim, C. S., Hwang, C. K., Choi, H. S., Song, K. Y., Law, P.-Y., Wei, L.-N., Loh, H. H.
(2004). Neuron-restrictive Silencer Factor (NRSF) Functions as a Repressor in Neuronal Cells to Regulate the {micro} Opioid Receptor Gene. J. Biol. Chem.
279: 46464-46473
[Abstract]
[Full Text]
-
Bruce, A. W., Donaldson, I. J., Wood, I. C., Yerbury, S. A., Sadowski, M. I., Chapman, M., Gottgens, B., Buckley, N. J.
(2004). Genome-wide analysis of repressor element 1 silencing transcription factor/neuron-restrictive silencing factor (REST/NRSF) target genes. Proc. Natl. Acad. Sci. USA
101: 10458-10463
[Abstract]
[Full Text]
-
Belyaev, N. D., Wood, I. C., Bruce, A. W., Street, M., Trinh, J.-B., Buckley, N. J.
(2004). Distinct RE-1 Silencing Transcription Factor-containing Complexes Interact with Different Target Genes. J. Biol. Chem.
279: 556-561
[Abstract]
[Full Text]
-
Runker, A. E., Bartsch, U., Nave, K.-A., Schachner, M.
(2003). The C264Y Missense Mutation in the Extracellular Domain of L1 Impairs Protein Trafficking In Vitro and In Vivo. J. Neurosci.
23: 277-286
[Abstract]
[Full Text]
-
Roopra, A., Huang, Y., Dingledine, R.
(2001). Neurological Disease: Listening to Gene Silencers. Mol. Interv.
1: 219-228
[Abstract]
[Full Text]
-
Kuwahara, K., Saito, Y., Ogawa, E., Takahashi, N., Nakagawa, Y., Naruse, Y., Harada, M., Hamanaka, I., Izumi, T., Miyamoto, Y., Kishimoto, I., Kawakami, R., Nakanishi, M., Mori, N., Nakao, K.
(2001). The Neuron-Restrictive Silencer Element-Neuron-Restrictive Silencer Factor System Regulates Basal and Endothelin 1-Inducible Atrial Natriuretic Peptide Gene Expression in Ventricular Myocytes. Mol. Cell. Biol.
21: 2085-2097
[Abstract]
[Full Text]
-
Paquette, A. J., Perez, S. E., Anderson, D. J.
(2000). Constitutive expression of the neuron-restrictive silencer factor (NRSF)/REST in differentiating neurons disrupts neuronal gene expression and causes axon pathfinding errors in vivo. Proc. Natl. Acad. Sci. USA
97: 12318-12323
[Abstract]
[Full Text]
-
Calmont, A., Reichwald, K., Ronco, P., Rossert, J.
(2000). Identification of a Short cis-Acting Element in the Human Vasopressin Type 2 Receptor Gene Which Confers High-Level Expression of a Reporter Gene Specifically in Collecting Duct Cells. Mol. Endocrinol.
14: 1682-1695
[Abstract]
[Full Text]
-
Kenwrick, S., Watkins, A., Angelis, E. D.
(2000). Neural cell recognition molecule L1: relating biological complexity to human disease mutations. Hum Mol Genet
9: 879-886
[Abstract]
[Full Text]
-
Grimes, J. A., Nielsen, S. J., Battaglioli, E., Miska, E. A., Speh, J. C., Berry, D. L., Atouf, F., Holdener, B. C., Mandel, G., Kouzarides, T.
(2000). The Co-repressor mSin3A Is a Functional Component of the REST-CoREST Repressor Complex. J. Biol. Chem.
275: 9461-9467
[Abstract]
[Full Text]
-
Roopra, A., Sharling, L., Wood, I. C., Briggs, T., Bachfischer, U., Paquette, A. J., Buckley, N. J.
(2000). Transcriptional Repression by Neuron-Restrictive Silencer Factor Is Mediated via the Sin3-Histone Deacetylase Complex. Mol. Cell. Biol.
20: 2147-2157
[Abstract]
[Full Text]
-
Naruse, Y., Aoki, T., Kojima, T., Mori, N.
(1999). Neural restrictive silencer factor recruits mSin3 and histone deacetylase complex to repress neuron-specific target genes. Proc. Natl. Acad. Sci. USA
96: 13691-13696
[Abstract]
[Full Text]
-
Meech, R., Kallunki, P., Edelman, G. M., Jones, F. S.
(1999). A binding site for homeodomain and Pax proteins is necessary for L1 cell adhesion molecule gene expression by Pax-6 and bone morphogenetic proteins. Proc. Natl. Acad. Sci. USA
96: 2420-2425
[Abstract]
[Full Text]
-
Timmusk, T., Palm, K., Lendahl, U., Metsis, M.
(1999). Brain-derived Neurotrophic Factor Expression in Vivo Is under the Control of Neuron-restrictive Silencer Element. J. Biol. Chem.
274: 1078-1084
[Abstract]
[Full Text]
-
Debiec, H., Christensen, E. I., Ronco, P. M.
(1998). The Cell Adhesion Molecule L1 Is Developmentally Regulated in the Renal Epithelium and Is Involved in Kidney Branching Morphogenesis. JCB
143: 2067-2079
[Abstract]
[Full Text]
-
Thiel, G., Lietz, M., Cramer, M.
(1998). Biological Activity and Modular Structure of RE-1-silencing Transcription Factor (REST), a Repressor of Neuronal Genes. J. Biol. Chem.
273: 26891-26899
[Abstract]
[Full Text]
-
Kallunki, P., Edelman, G. M., Jones, F. S.
(1998). The neural restrictive silencer element can act as both a repressor and enhancer of L1 cell adhesion molecule gene expression during postnatal development. Proc. Natl. Acad. Sci. USA
95: 3233-3238
[Abstract]
[Full Text]
-
De Gois, S., Houhou, L., Oda, Y., Corbex, M., Pajak, F., Thevenot, E., Vodjdani, G., Mallet, J., Berrard, S.
(2000). Is RE1/NRSE a Common cis-Regulatory Sequence for ChAT and VAChT Genes?. J. Biol. Chem.
275: 36683-36690
[Abstract]
[Full Text]
-
Seth, K. A., Majzoub, J. A.
(2001). Repressor Element Silencing Transcription Factor/Neuron-restrictive Silencing Factor (REST/NRSF) Can Act as an Enhancer as Well as a Repressor of Corticotropin-releasing Hormone Gene Transcription. J. Biol. Chem.
276: 13917-13923
[Abstract]
[Full Text]
-
Shimojo, M., Lee, J.-H., Hersh, L. B.
(2001). Role of Zinc Finger Domains of the Transcription Factor Neuron-restrictive Silencer Factor/Repressor Element-1 Silencing Transcription Factor in DNA Binding and Nuclear Localization. J. Biol. Chem.
276: 13121-13126
[Abstract]
[Full Text]
-
Koenigsberger, C., Chicca, J. J. II, Amoureux, M.-C., Edelman, G. M., Jones, F. S.
(2000). Differential regulation by multiple promoters of the gene encoding the neuron-restrictive silencer factor. Proc. Natl. Acad. Sci. USA
97: 2291-2296
[Abstract]
[Full Text]