Differentiation of a Catecholaminergic CNS Cell Line Modifies Tyrosine Hydroxylase Transcriptional Regulation
| Autor: | Dona M. Chikaraishi, Meredith Lazaroff, Yanping Qi |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Central Nervous System
Chloramphenicol O-Acetyltransferase Transcription Genetic Tyrosine 3-Monooxygenase Cellular differentiation DNA Mutational Analysis Biology Biochemistry Gene Expression Regulation Enzymologic Mice Cellular and Molecular Neuroscience Catecholamines Genes Reporter Transcription (biology) Transcriptional regulation Animals Cell Line Transformed Neurons Reporter gene Tyrosine hydroxylase Cell Differentiation Blood Proteins Transfection Cell biology AP-1 transcription factor Enhancer Elements Genetic Cell culture |
| Zdroj: | Journal of Neurochemistry. 71:51-59 |
| ISSN: | 1471-4159 0022-3042 |
| DOI: | 10.1046/j.1471-4159.1998.71010051.x |
| Popis: | Recently, a tyrosine hydroxylase (TH)-expressing CNS-derived cell line, CAD, was obtained that is capable of undergoing reversible morphological differentiation. The isolation of the CAD line allowed us to ask whether different DNA regulatory elements direct TH transcription when cells are growing and undifferentiated versus postmitotic and differentiated. To this end, we compared expression of a transiently transfected bacterial chloramphenicol acetyltransferase reporter gene under the transcriptional control of TH 5' flanking DNA in CAD cells grown in the presence and absence of serum. Mutational analysis indicates that CAD cells differently regulate TH transcription depending on their state of differentiation. In both states, the cyclic AMP response element and AP1 site each activate transcription. However, in undifferentiated cells, the dyad/E-box element represses expression by approximately 2.7-fold, whereas it modestly activates transcription in differentiated cells. The role of the dyad/ E-box as a repressor correlates well with the two- to threefold lower amount of endogenous TH protein present in the undifferentiated CAD cells. This study demonstrates the differential use of TH DNA regulatory elements in proliferating, undifferentiated and nonproliferating, differentiated immortalized neuronal cells. |
| Databáze: | OpenAIRE |
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