AUF1 is expressed in the developing brain, binds to AT-rich double-stranded DNA, and regulates enkephalin gene expression

Albert Dobi, Marianna Szemes, Cheol Lee, M. Palkóvits, Francis Lim, Andrea Gyorgy, Mark A. Mahan, Denes V. Agoston

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

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 ∼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.

Original languageEnglish
Pages (from-to)28889-28900
Number of pages12
JournalJournal of Biological Chemistry
Volume281
Issue number39
DOIs
Publication statusPublished - Sep 29 2006

Fingerprint

Enkephalins
Gene expression
Brain
Genes
Gene Expression
DNA
AT Rich Sequence
Rats
Heterogeneous-Nuclear Ribonucleoprotein D
DNA sequences
Cell culture
Neurons
Neurotransmitter Agents
Protein Isoforms
Immunohistochemistry
Messenger RNA
Peptides
hnRNP D0

ASJC Scopus subject areas

  • Biochemistry

Cite this

AUF1 is expressed in the developing brain, binds to AT-rich double-stranded DNA, and regulates enkephalin gene expression. / Dobi, Albert; Szemes, Marianna; Lee, Cheol; Palkóvits, M.; Lim, Francis; Gyorgy, Andrea; Mahan, Mark A.; Agoston, Denes V.

In: Journal of Biological Chemistry, Vol. 281, No. 39, 29.09.2006, p. 28889-28900.

Research output: Contribution to journalArticle

Dobi, Albert ; Szemes, Marianna ; Lee, Cheol ; Palkóvits, M. ; Lim, Francis ; Gyorgy, Andrea ; Mahan, Mark A. ; Agoston, Denes V. / AUF1 is expressed in the developing brain, binds to AT-rich double-stranded DNA, and regulates enkephalin gene expression. In: Journal of Biological Chemistry. 2006 ; Vol. 281, No. 39. pp. 28889-28900.
@article{4f9f58ed586346a7b1d2b7209af33f36,
title = "AUF1 is expressed in the developing brain, binds to AT-rich double-stranded DNA, and regulates enkephalin gene expression",
abstract = "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 ∼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.",
author = "Albert Dobi and Marianna Szemes and Cheol Lee and M. Palk{\'o}vits and Francis Lim and Andrea Gyorgy and Mahan, {Mark A.} and Agoston, {Denes V.}",
year = "2006",
month = "9",
day = "29",
doi = "10.1074/jbc.M511858200",
language = "English",
volume = "281",
pages = "28889--28900",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "39",

}

TY - JOUR

T1 - AUF1 is expressed in the developing brain, binds to AT-rich double-stranded DNA, and regulates enkephalin gene expression

AU - Dobi, Albert

AU - Szemes, Marianna

AU - Lee, Cheol

AU - Palkóvits, M.

AU - Lim, Francis

AU - Gyorgy, Andrea

AU - Mahan, Mark A.

AU - Agoston, Denes V.

PY - 2006/9/29

Y1 - 2006/9/29

N2 - 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 ∼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.

AB - 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 ∼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.

UR - http://www.scopus.com/inward/record.url?scp=33749407650&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33749407650&partnerID=8YFLogxK

U2 - 10.1074/jbc.M511858200

DO - 10.1074/jbc.M511858200

M3 - Article

C2 - 16769718

AN - SCOPUS:33749407650

VL - 281

SP - 28889

EP - 28900

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 39

ER -