Transcriptional Control of the Human Sodium-coupled Neutral Amino Acid Transporter System A Gene by Amino Acid Availability Is Mediated by an Intronic Element

Stela S. Palii, Hong Chen, Michael S. Kilberg

Research output: Contribution to journalArticle

Abstract

System A amino acid transporter (SNAT2) gene expression is up-regulated at the transcriptional level in response to amino acid deprivation. Functional analysis of genomic fragments 5′ upstream of the transcription start site, for both human and mouse SNAT2 genes showed that these regions exhibit promoter activity, but were amino acid unresponsive. However, when the human and mouse constructs were extended to include intron 1, it was observed that the rate of transcription was increased following amino acid deprivation. Deletion analysis of the human gene identified an intron 1 sequence spanning 54 nucleotides that was sufficient for conferring amino acid-dependent regulation to a minimal SNAT2 promoter. Alignment of the corresponding region from the human, mouse, and rat genomes revealed three highly conserved sequences. From site-directed mutagenesis, it was concluded that one of these sites functions as an amino acid response element (AARE) to regulate transcription. The core sequence of this site is identical to the AARE in the human CHOP gene. The SNAT2 AARE, along with a nearby conserved CAAT box, has enhancer activity in that it functions in an orientation and position independent manner, and it confers regulated transcription to a heterologous promoter.

Original languageEnglish (US)
Pages (from-to)3463-3471
Number of pages9
JournalJournal of Biological Chemistry
Volume279
Issue number5
DOIs
StatePublished - Jan 30 2004
Externally publishedYes

Fingerprint

Neutral Amino Acid Transport Systems
Genes
Sodium
Availability
Amino Acids
Response Elements
Transcription
Introns
Amino Acid Transport Systems
Mutagenesis
Functional analysis
Conserved Sequence
Transcription Initiation Site
Site-Directed Mutagenesis
Genetic Promoter Regions
Gene expression
Rats
Nucleotides
Genome
Gene Expression

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Transcriptional Control of the Human Sodium-coupled Neutral Amino Acid Transporter System A Gene by Amino Acid Availability Is Mediated by an Intronic Element. / Palii, Stela S.; Chen, Hong; Kilberg, Michael S.

In: Journal of Biological Chemistry, Vol. 279, No. 5, 30.01.2004, p. 3463-3471.

Research output: Contribution to journalArticle

@article{2299f6703a6240b093b9f5ec04ba66c4,
title = "Transcriptional Control of the Human Sodium-coupled Neutral Amino Acid Transporter System A Gene by Amino Acid Availability Is Mediated by an Intronic Element",
abstract = "System A amino acid transporter (SNAT2) gene expression is up-regulated at the transcriptional level in response to amino acid deprivation. Functional analysis of genomic fragments 5′ upstream of the transcription start site, for both human and mouse SNAT2 genes showed that these regions exhibit promoter activity, but were amino acid unresponsive. However, when the human and mouse constructs were extended to include intron 1, it was observed that the rate of transcription was increased following amino acid deprivation. Deletion analysis of the human gene identified an intron 1 sequence spanning 54 nucleotides that was sufficient for conferring amino acid-dependent regulation to a minimal SNAT2 promoter. Alignment of the corresponding region from the human, mouse, and rat genomes revealed three highly conserved sequences. From site-directed mutagenesis, it was concluded that one of these sites functions as an amino acid response element (AARE) to regulate transcription. The core sequence of this site is identical to the AARE in the human CHOP gene. The SNAT2 AARE, along with a nearby conserved CAAT box, has enhancer activity in that it functions in an orientation and position independent manner, and it confers regulated transcription to a heterologous promoter.",
author = "Palii, {Stela S.} and Hong Chen and Kilberg, {Michael S.}",
year = "2004",
month = "1",
day = "30",
doi = "10.1074/jbc.M310483200",
language = "English (US)",
volume = "279",
pages = "3463--3471",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "5",

}

TY - JOUR

T1 - Transcriptional Control of the Human Sodium-coupled Neutral Amino Acid Transporter System A Gene by Amino Acid Availability Is Mediated by an Intronic Element

AU - Palii, Stela S.

AU - Chen, Hong

AU - Kilberg, Michael S.

PY - 2004/1/30

Y1 - 2004/1/30

N2 - System A amino acid transporter (SNAT2) gene expression is up-regulated at the transcriptional level in response to amino acid deprivation. Functional analysis of genomic fragments 5′ upstream of the transcription start site, for both human and mouse SNAT2 genes showed that these regions exhibit promoter activity, but were amino acid unresponsive. However, when the human and mouse constructs were extended to include intron 1, it was observed that the rate of transcription was increased following amino acid deprivation. Deletion analysis of the human gene identified an intron 1 sequence spanning 54 nucleotides that was sufficient for conferring amino acid-dependent regulation to a minimal SNAT2 promoter. Alignment of the corresponding region from the human, mouse, and rat genomes revealed three highly conserved sequences. From site-directed mutagenesis, it was concluded that one of these sites functions as an amino acid response element (AARE) to regulate transcription. The core sequence of this site is identical to the AARE in the human CHOP gene. The SNAT2 AARE, along with a nearby conserved CAAT box, has enhancer activity in that it functions in an orientation and position independent manner, and it confers regulated transcription to a heterologous promoter.

AB - System A amino acid transporter (SNAT2) gene expression is up-regulated at the transcriptional level in response to amino acid deprivation. Functional analysis of genomic fragments 5′ upstream of the transcription start site, for both human and mouse SNAT2 genes showed that these regions exhibit promoter activity, but were amino acid unresponsive. However, when the human and mouse constructs were extended to include intron 1, it was observed that the rate of transcription was increased following amino acid deprivation. Deletion analysis of the human gene identified an intron 1 sequence spanning 54 nucleotides that was sufficient for conferring amino acid-dependent regulation to a minimal SNAT2 promoter. Alignment of the corresponding region from the human, mouse, and rat genomes revealed three highly conserved sequences. From site-directed mutagenesis, it was concluded that one of these sites functions as an amino acid response element (AARE) to regulate transcription. The core sequence of this site is identical to the AARE in the human CHOP gene. The SNAT2 AARE, along with a nearby conserved CAAT box, has enhancer activity in that it functions in an orientation and position independent manner, and it confers regulated transcription to a heterologous promoter.

UR - http://www.scopus.com/inward/record.url?scp=0942265548&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0942265548&partnerID=8YFLogxK

U2 - 10.1074/jbc.M310483200

DO - 10.1074/jbc.M310483200

M3 - Article

C2 - 14623874

AN - SCOPUS:0942265548

VL - 279

SP - 3463

EP - 3471

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 5

ER -