AUF1 Is Expressed in the Developing Brain, Binds to AT-rich Double-stranded DNA, and Regulates Enkephalin Gene Expression
| Autor: | Francis Lim, Denes V. Agoston, Marianna Szemes, Mark A. Mahan, Albert Dobi, Cheol Lee, Miklos Palkovits, Andrea Gyorgy |
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| Rok vydání: | 2006 |
| Předmět: |
Gene isoform
endocrine system Enkephalin Molecular Sequence Data Repressor Biology Biochemistry DNA sequencing Mice chemistry.chemical_compound Gene expression Animals Humans Heterogeneous Nuclear Ribonucleoprotein D0 Heterogeneous-Nuclear Ribonucleoprotein D Neurotransmitter Molecular Biology Gene Base Sequence Brain Gene Expression Regulation Developmental DNA Enkephalins Cell Biology Immunohistochemistry Molecular biology Rats DNA-Binding Proteins chemistry |
| Zdroj: | Journal of Biological Chemistry. 281:28889-28900 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m511858200 |
| Popis: | During our search for transcriptional regulators that control the developmentally regulated expression of the enkephalin (ENK) gene, we identified AUF1. ENK, a peptide neurotransmitter, displays precise cell-specific expression in the adult brain. AUF1 (also known as heterogeneous nuclear ribonucleoprotein D) has been known to regulate gene expression through altering the stability of AU-rich mRNAs. We show here that in the developing brain AUF1 proteins are expressed in a spatiotemporally defined manner, and p37 and p40/42 isoforms bind to an AT-rich double-stranded (ds) DNA element of the rat ENK (rENK) gene. This AT-rich dsDNA sequence acts as a cis-regulatory DNA element and is involved in regulating the cell-specific expression of the ENK gene in primary neuronal cultures. The AT-rich dsDNA elements are present at approximately 2.5 kb 5'upstream of the rat, human, and mouse ENK genes. AUF1 proteins are shown here to provide direct interaction between these upstream AT-rich DNA sequences and the TATA region of the rENK gene. Double immunohistochemistry demonstrated that in the developing brain AUF1 proteins are expressed by proliferating neural progenitors and by differentiating neurons populating brain regions, which will not express the ENK gene in the adult, suggesting a repressor role for AUF1 proteins during enkephalinergic differentiation. Their subnuclear distribution and interactions with AT-rich DNA suggest that in the developing brain they can be involved in complex nuclear regulatory mechanisms controlling the development- and cell-specific expression of the ENK gene. |
| Databáze: | OpenAIRE |
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