Basic Transcription Element-binding Protein (BTEB) Is a Thyroid Hormone-regulated Gene in the Developing Central Nervous System

Thyroid hormone (3,5,3′-triiodothyronine; T3) is essential for normal development of the vertebrate brain, influencing diverse processes such as neuronal migration, myelin formation, axonal maturation, and dendritic outgrowth. We have identified basic transcription element-binding protein (BTEB), a small GC box-binding protein, as a T3-regulated gene in developing rat brain. BTEB mRNA levels in cerebral cortex exhibit developmental regulation and thyroid hormone dependence. T3 regulation of BTEB mRNA is neural cell-specific, being up-regulated in primary cultures of embryonic neurons (E16) and in neonatal astrocytes (P2), but not in neonatal oligodendrocytes (P2). T3 rapidly up-regulated BTEB mRNA in neuro-2a cells engineered to express thyroid hormone receptor (TR) β1 but not in cells expressing TRα1, suggesting that the regulation of this gene is specific to the TRβ1 isoform. Several lines of evidence support a transcriptional action of T3 on BTEB gene expression. Overexpression of BTEB in Neuro-2a cells dramatically increased the number and length of neurites in a dose-dependent manner suggesting a role for this transcription factor in neuronal process formation. However, other T3-dependent changes were not altered;i.e. overexpression of BTEB had no effect on the rate of cell proliferation nor on the expression of acetylcholinesterase activity.

[1]  G. Labourdette,et al.  Effects of acidic and basic fibroblast growth factors on proliferation and maturation of cultured rat oligodendrocytes , 1989, International Journal of Developmental Neuroscience.

[2]  R. Garesse,et al.  Thyroid hormone-regulated brain mitochondrial genes revealed by differential cDNA cloning. , 1995, The Journal of clinical investigation.

[3]  D. Stott.  Analysis of transcriptional initiation in isolated nuclei. , 1991, Methods in molecular biology.

[4]  J. Puymirat,et al.  Expression of thyroid hormone receptors mRNAs in rat cerebral hemisphere neuronal cultures. , 1992, Brain research. Developmental brain research.

[5]  C. Thompson.  Thyroid Hormone-Responsive Genes in Developing Cerebellum Include a Novel Synaptotagmin and a hairless Homolog , 1996, The Journal of Neuroscience.

[6]  J. Dussault,et al.  Thyroid hormones and brain development. , 1987, Annual review of physiology.

[7]  J. Caubín,et al.  Identification of the mitochondrial NADH dehydrogenase subunit 3 (ND3) as a thyroid hormone regulated gene by whole genome PCR analysis. , 1995, Biochemical and biophysical research communications.

[8]  O. H. Lowry,et al.  Protein measurement with the Folin phenol reagent. , 1951, The Journal of biological chemistry.

[9]  Zhou Wang,et al.  A gene expression screen. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[10]  K. Umesono,et al.  The nuclear receptor superfamily: The second decade , 1995, Cell.

[11]  J. Puymirat,et al.  Immunocytochemical localization of nuclear 3,5,3'-triiodothyronine (L-T3) receptors in astrocyte cultures. , 1989, Brain research. Developmental brain research.

[12]  H. Samuels,et al.  Depletion of L-3,5,3'-triiodothyronine and L-thyroxine in euthyroid calf serum for use in cell culture studies of the action of thyroid hormone. , 1979, Endocrinology.

[13]  S. P. Porterfield,et al.  The role of thyroid hormones in prenatal and neonatal neurological development--current perspectives. , 1993, Endocrine reviews.

[14]  A. Vigny,et al.  Triiodothyronine enhances the morphological maturation of dopaminergic neurons from fetal mouse hypothalamus cultured in serum-free medium , 1983, Neuroscience.

[15]  J. Puymirat,et al.  Thyroid Hormones Stabilize Acetylcholinesterase mRNA in Neuro-2A Cells That Overexpress the β1 Thyroid Receptor (*) , 1995, The Journal of Biological Chemistry.

[16]  J. Jameson,et al.  Cyclic AMP (cAMP) effects on chorionic gonadotropin gene transcription and mRNA stability: labile proteins mediate basal expression whereas stable proteins mediate cAMP stimulation. , 1989, Molecular endocrinology.

[17]  B. O’Malley,et al.  Molecular mechanisms of action of steroid/thyroid receptor superfamily members. , 1994, Annual review of biochemistry.

[18]  J. Sambrook,et al.  Molecular Cloning: A Laboratory Manual , 2001 .

[19]  H. Stunnenberg,et al.  Thyroid hormone‐dependent transcriptional repression of neural cell adhesion molecule during brain maturation. , 1996, The EMBO journal.

[20]  Y. Fujii‐Kuriyama,et al.  Two regulatory proteins that bind to the basic transcription element (BTE), a GC box sequence in the promoter region of the rat P‐4501A1 gene. , 1992, The EMBO journal.

[21]  J. Heard.  Gene transfer and expression protocols: (Methods in Molecular Biology Series, vol 7) edited by Edward J Murray, Humana Press, 1991, xiii + 439 pp , 1992 .

[22]  J. Puymirat,et al.  Overexpression of the beta 1 thyroid receptor induces differentiation in neuro-2a cells. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[23]  Yunbo Shi,et al.  Thyroid Hormone-dependent Gene Expression Program for Xenopus Neural Development* , 1997, The Journal of Biological Chemistry.

[24]  J. Puymirat,et al.  Thyroid hormone up‐regulates thyroid hormone receptor β gene expression in rat cerebral hemisphere astrocyte cultures , 1993, Glia.

[25]  J. Puymirat,et al.  Evolution of triiodothyronine nuclear binding sites in hypothalamic serum-free cultures: Evidence for their presence in neurons and astrocytes , 1986, Neuroscience Letters.

[27]  Y. Fujii‐Kuriyama,et al.  Cell-specific translational control of transcription factor BTEB expression. The role of an upstream AUG in the 5'-untranslated region. , 1994, The Journal of biological chemistry.

[28]  E. Murray.  Gene Transfer and Expression Protocols , 1991 .

[29]  J. Sutcliffe,et al.  p1B15: a cDNA clone of the rat mRNA encoding cyclophilin. , 1988, DNA.

[30]  E. Brown,et al.  A rapid and simple one step method for isolation of poly(A)+ RNA from cells in monolayer. , 1990, Endocrinology.

[31]  J. Puymirat,et al.  Influence of triiodothyronine (L-T3) on the morphological and biochemical development of fetal brain acetylcholinesterase-positive neurons cultured in a chemically defined medium. , 1988, Brain research.

[32]  F. Denizot,et al.  Rapid colorimetric assay for cell growth and survival. Modifications to the tetrazolium dye procedure giving improved sensitivity and reliability. , 1986, Journal of immunological methods.

[33]  J. Sutcliffe,et al.  Effects of neonatal hypothyroidism on rat brain gene expression. , 1991, Molecular endocrinology.

[34]  R. Faure,et al.  Ontogenesis of nuclear T3 receptors in primary cultured astrocytes and neurons , 1986, Brain Research.

[35]  P. Chomczyński,et al.  Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. , 1987, Analytical biochemistry.

[36]  C. Thompson,et al.  The product of a thyroid hormone-responsive gene interacts with thyroid hormone receptors. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[37]  J. Puymirat.  Thyroid receptors in the rat brain , 1992, Progress in Neurobiology.

[38]  J. Puymirat,et al.  Oligodendrocyte maturation and progenitor cell proliferation are independently regulated by thyroid hormone , 1997, Glia.

[39]  Z. Wang,et al.  The thyroid hormone-induced tail resorption program during Xenopus laevis metamorphosis. , 1996, Proceedings of the National Academy of Sciences of the United States of America.