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Searching for tissue-specific expression pattern-linked nucleotides of UGT1A isoforms.

Zhang W, Liu W, Innocenti F, Ratain MJ - PLoS ONE (2007)

Bottom Line: The tissue-specific expression patterns were observed in 13 tissues.To understand the regulation mechanism that is responsible for the tissue-specific expression patterns, we scanned the DNA sequence alignments of the putative promoter regions, exon 1 sequences and intron 1 sequences for those expression-pattern-linked nucleotides.Using one of the expression-pattern-linked nucleotides for livers as an example, we showed that a database comprised of these expression-pattern-linked nucleotides could be used to generate focused hypotheses on the problem of tissue-specific expression, which is critical for tissue-specific pharmacodynamics of anticancer drugs.

View Article: PubMed Central - PubMed

Affiliation: Section of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, Illinois, United States of America.

ABSTRACT
UDP-glucuronosyltransferases 1A isoforms belong to a superfamily of microsomal enzymes responsible for glucuronidation of numerous endogenous and exogenous compounds. The nine functional UGT1A isoforms are encoded by a single UGT1A gene locus with multiple first exons. The expression of the UGT1A transcripts was measured by quantitative RT-PCR in 23 normal human tissues. The tissue-specific expression patterns were observed in 13 tissues. To understand the regulation mechanism that is responsible for the tissue-specific expression patterns, we scanned the DNA sequence alignments of the putative promoter regions, exon 1 sequences and intron 1 sequences for those expression-pattern-linked nucleotides. Using one of the expression-pattern-linked nucleotides for livers as an example, we showed that a database comprised of these expression-pattern-linked nucleotides could be used to generate focused hypotheses on the problem of tissue-specific expression, which is critical for tissue-specific pharmacodynamics of anticancer drugs.

Show MeSH
Expression of UGT1A isoforms among multiple human tissue samples. For each functional UGT1A isoform (A through I), an example for the PCR gels for expression in multiple human tissues together with molecular weight markers is shown.
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pone-0000396-g001: Expression of UGT1A isoforms among multiple human tissue samples. For each functional UGT1A isoform (A through I), an example for the PCR gels for expression in multiple human tissues together with molecular weight markers is shown.

Mentions: We measured the expression levels of the nine functional UGT1A isoforms in 23 normal tissues. UGT1A genes were not expressed in 10 tissues (brain, skeletal muscle, spleen, uterus, mammary gland, pituitary body, bone marrow, lymph node, leukocyte and all blood fractions), while the tissue-specific expression patterns were observed in other 13 tissues, among which placenta and lung had only one expressed isoform (UGT1A6) (Table 1). Some examples of the expression of UGT1A isoforms among multiple human tissue samples are provided in Figure 1. The relative expression levels based on the density of PCR products of the isoforms in each tissue are shown in Table 1. Some published tissue-specific expression patterns have been confirmed in our RT-PCR expression data. For examples, our data confirmed that UGT1A1, UGT1A3, UGT1A4, UGT1A6 and UGT1A9 are expressed in livers [3], [9]–[12], UGT1A6 is expressed in lungs [13], UGT1A7 is expressed in kidneys [13], and UGT1A10 is expressed in intestines [7].


Searching for tissue-specific expression pattern-linked nucleotides of UGT1A isoforms.

Zhang W, Liu W, Innocenti F, Ratain MJ - PLoS ONE (2007)

Expression of UGT1A isoforms among multiple human tissue samples. For each functional UGT1A isoform (A through I), an example for the PCR gels for expression in multiple human tissues together with molecular weight markers is shown.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC1851988&req=5

pone-0000396-g001: Expression of UGT1A isoforms among multiple human tissue samples. For each functional UGT1A isoform (A through I), an example for the PCR gels for expression in multiple human tissues together with molecular weight markers is shown.
Mentions: We measured the expression levels of the nine functional UGT1A isoforms in 23 normal tissues. UGT1A genes were not expressed in 10 tissues (brain, skeletal muscle, spleen, uterus, mammary gland, pituitary body, bone marrow, lymph node, leukocyte and all blood fractions), while the tissue-specific expression patterns were observed in other 13 tissues, among which placenta and lung had only one expressed isoform (UGT1A6) (Table 1). Some examples of the expression of UGT1A isoforms among multiple human tissue samples are provided in Figure 1. The relative expression levels based on the density of PCR products of the isoforms in each tissue are shown in Table 1. Some published tissue-specific expression patterns have been confirmed in our RT-PCR expression data. For examples, our data confirmed that UGT1A1, UGT1A3, UGT1A4, UGT1A6 and UGT1A9 are expressed in livers [3], [9]–[12], UGT1A6 is expressed in lungs [13], UGT1A7 is expressed in kidneys [13], and UGT1A10 is expressed in intestines [7].

Bottom Line: The tissue-specific expression patterns were observed in 13 tissues.To understand the regulation mechanism that is responsible for the tissue-specific expression patterns, we scanned the DNA sequence alignments of the putative promoter regions, exon 1 sequences and intron 1 sequences for those expression-pattern-linked nucleotides.Using one of the expression-pattern-linked nucleotides for livers as an example, we showed that a database comprised of these expression-pattern-linked nucleotides could be used to generate focused hypotheses on the problem of tissue-specific expression, which is critical for tissue-specific pharmacodynamics of anticancer drugs.

View Article: PubMed Central - PubMed

Affiliation: Section of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, Illinois, United States of America.

ABSTRACT
UDP-glucuronosyltransferases 1A isoforms belong to a superfamily of microsomal enzymes responsible for glucuronidation of numerous endogenous and exogenous compounds. The nine functional UGT1A isoforms are encoded by a single UGT1A gene locus with multiple first exons. The expression of the UGT1A transcripts was measured by quantitative RT-PCR in 23 normal human tissues. The tissue-specific expression patterns were observed in 13 tissues. To understand the regulation mechanism that is responsible for the tissue-specific expression patterns, we scanned the DNA sequence alignments of the putative promoter regions, exon 1 sequences and intron 1 sequences for those expression-pattern-linked nucleotides. Using one of the expression-pattern-linked nucleotides for livers as an example, we showed that a database comprised of these expression-pattern-linked nucleotides could be used to generate focused hypotheses on the problem of tissue-specific expression, which is critical for tissue-specific pharmacodynamics of anticancer drugs.

Show MeSH