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Genomic and neural analysis of the estradiol-synthetic pathway in the zebra finch.

London SE, Clayton DF - BMC Neurosci (2010)

Bottom Line: We found very little qualitative overlap in predicted transcription factor binding sites in the genes for two cholesterol transport proteins, the 18 kDa cholesterol transport protein (TSPO) and steroidogenic acute regulatory protein (StAR).We therefore performed in situ hybridization for TSPO and found that its mRNA was not always detected in brain regions where StAR and steroidogenic enzymes were previously shown to be expressed.Coordinated transcription of multiple steroidogenic genes is possible, but results were inconsistent with the hypothesis that StAR and TSPO mRNAs are co-regulated.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL, USA. slondon@illinois.edu

ABSTRACT

Background: Steroids are small molecule hormones derived from cholesterol. Steroids affect many tissues, including the brain. In the zebra finch, estrogenic steroids are particularly interesting because they masculinize the neural circuit that controls singing and their synthesis in the brain is modulated by experience. Here, we analyzed the zebra finch genome assembly to assess the content, conservation, and organization of genes that code for components of the estrogen-synthetic pathway and steroid nuclear receptors. Based on these analyses, we also investigated neural expression of a cholesterol transport protein gene in the context of song neurobiology.

Results: We present sequence-based analysis of twenty steroid-related genes using the genome assembly and other resources. Generally, zebra finch genes showed high homology to genes in other species. The diversity of steroidogenic enzymes and receptors may be lower in songbirds than in mammals; we were unable to identify all known mammalian isoforms of the 3beta-hydroxysteroid dehydrogenase and 17beta-hydroxysteroid dehydrogenase families in the zebra finch genome assembly, and not all splice sites described in mammals were identified in the corresponding zebra finch genes. We did identify two factors, Nobox and NR1H2-RXR, that may be important for coordinated transcription of multiple steroid-related genes. We found very little qualitative overlap in predicted transcription factor binding sites in the genes for two cholesterol transport proteins, the 18 kDa cholesterol transport protein (TSPO) and steroidogenic acute regulatory protein (StAR). We therefore performed in situ hybridization for TSPO and found that its mRNA was not always detected in brain regions where StAR and steroidogenic enzymes were previously shown to be expressed. Also, transcription of TSPO, but not StAR, may be regulated by the experience of hearing song.

Conclusions: The genes required for estradiol synthesis and action are represented in the zebra finch genome assembly, though the complement of steroidogenic genes may be smaller in birds than in mammals. Coordinated transcription of multiple steroidogenic genes is possible, but results were inconsistent with the hypothesis that StAR and TSPO mRNAs are co-regulated. Integration of genomic and neuroanatomical analyses will continue to provide insights into the evolution and function of steroidogenesis in the songbird brain.

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Unrooted phylogenetic tree of HSD17B predicted protein sequences. We identified nine HSD17B genes in the zebra finch assembly; these predicted proteins segregated with the same enzyme type in chicken and the other species. The unrooted tree models some enzymes (HSD17B4 and 7) as unique branches. Enzyme types predicted to be evolutionarily related (HSD17B3 and 12, and HSD17B2 and 6), are shown to be preserved in the zebra finch. Bootstrap support values are at branch points. Scale bar denotes substitution rate. zf = zebra finch, ch = chicken, h = human, m = mouse, dan = zebrafish, iso = isoform.
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Figure 4: Unrooted phylogenetic tree of HSD17B predicted protein sequences. We identified nine HSD17B genes in the zebra finch assembly; these predicted proteins segregated with the same enzyme type in chicken and the other species. The unrooted tree models some enzymes (HSD17B4 and 7) as unique branches. Enzyme types predicted to be evolutionarily related (HSD17B3 and 12, and HSD17B2 and 6), are shown to be preserved in the zebra finch. Bootstrap support values are at branch points. Scale bar denotes substitution rate. zf = zebra finch, ch = chicken, h = human, m = mouse, dan = zebrafish, iso = isoform.

Mentions: To look at the phylogenetic relationship among HSD17B predicted proteins, we used all annotated HSD17B genes in human, mouse, zebrafish, and chicken, plus those we identified in zebra finch (Figure 4). In general, the zebra finch proteins segregated with the same enzyme type in chicken and the other species. This analysis modeled HSD17B4 and HSD17B7 proteins as independent branches, not closely related to any other HSD17B enzyme. Several other protein types, however, showed more similarity to another. For example, the type 3 and 12 proteins were clustered together on the tree, as were types 2 and 6.


Genomic and neural analysis of the estradiol-synthetic pathway in the zebra finch.

London SE, Clayton DF - BMC Neurosci (2010)

Unrooted phylogenetic tree of HSD17B predicted protein sequences. We identified nine HSD17B genes in the zebra finch assembly; these predicted proteins segregated with the same enzyme type in chicken and the other species. The unrooted tree models some enzymes (HSD17B4 and 7) as unique branches. Enzyme types predicted to be evolutionarily related (HSD17B3 and 12, and HSD17B2 and 6), are shown to be preserved in the zebra finch. Bootstrap support values are at branch points. Scale bar denotes substitution rate. zf = zebra finch, ch = chicken, h = human, m = mouse, dan = zebrafish, iso = isoform.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2865489&req=5

Figure 4: Unrooted phylogenetic tree of HSD17B predicted protein sequences. We identified nine HSD17B genes in the zebra finch assembly; these predicted proteins segregated with the same enzyme type in chicken and the other species. The unrooted tree models some enzymes (HSD17B4 and 7) as unique branches. Enzyme types predicted to be evolutionarily related (HSD17B3 and 12, and HSD17B2 and 6), are shown to be preserved in the zebra finch. Bootstrap support values are at branch points. Scale bar denotes substitution rate. zf = zebra finch, ch = chicken, h = human, m = mouse, dan = zebrafish, iso = isoform.
Mentions: To look at the phylogenetic relationship among HSD17B predicted proteins, we used all annotated HSD17B genes in human, mouse, zebrafish, and chicken, plus those we identified in zebra finch (Figure 4). In general, the zebra finch proteins segregated with the same enzyme type in chicken and the other species. This analysis modeled HSD17B4 and HSD17B7 proteins as independent branches, not closely related to any other HSD17B enzyme. Several other protein types, however, showed more similarity to another. For example, the type 3 and 12 proteins were clustered together on the tree, as were types 2 and 6.

Bottom Line: We found very little qualitative overlap in predicted transcription factor binding sites in the genes for two cholesterol transport proteins, the 18 kDa cholesterol transport protein (TSPO) and steroidogenic acute regulatory protein (StAR).We therefore performed in situ hybridization for TSPO and found that its mRNA was not always detected in brain regions where StAR and steroidogenic enzymes were previously shown to be expressed.Coordinated transcription of multiple steroidogenic genes is possible, but results were inconsistent with the hypothesis that StAR and TSPO mRNAs are co-regulated.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL, USA. slondon@illinois.edu

ABSTRACT

Background: Steroids are small molecule hormones derived from cholesterol. Steroids affect many tissues, including the brain. In the zebra finch, estrogenic steroids are particularly interesting because they masculinize the neural circuit that controls singing and their synthesis in the brain is modulated by experience. Here, we analyzed the zebra finch genome assembly to assess the content, conservation, and organization of genes that code for components of the estrogen-synthetic pathway and steroid nuclear receptors. Based on these analyses, we also investigated neural expression of a cholesterol transport protein gene in the context of song neurobiology.

Results: We present sequence-based analysis of twenty steroid-related genes using the genome assembly and other resources. Generally, zebra finch genes showed high homology to genes in other species. The diversity of steroidogenic enzymes and receptors may be lower in songbirds than in mammals; we were unable to identify all known mammalian isoforms of the 3beta-hydroxysteroid dehydrogenase and 17beta-hydroxysteroid dehydrogenase families in the zebra finch genome assembly, and not all splice sites described in mammals were identified in the corresponding zebra finch genes. We did identify two factors, Nobox and NR1H2-RXR, that may be important for coordinated transcription of multiple steroid-related genes. We found very little qualitative overlap in predicted transcription factor binding sites in the genes for two cholesterol transport proteins, the 18 kDa cholesterol transport protein (TSPO) and steroidogenic acute regulatory protein (StAR). We therefore performed in situ hybridization for TSPO and found that its mRNA was not always detected in brain regions where StAR and steroidogenic enzymes were previously shown to be expressed. Also, transcription of TSPO, but not StAR, may be regulated by the experience of hearing song.

Conclusions: The genes required for estradiol synthesis and action are represented in the zebra finch genome assembly, though the complement of steroidogenic genes may be smaller in birds than in mammals. Coordinated transcription of multiple steroidogenic genes is possible, but results were inconsistent with the hypothesis that StAR and TSPO mRNAs are co-regulated. Integration of genomic and neuroanatomical analyses will continue to provide insights into the evolution and function of steroidogenesis in the songbird brain.

Show MeSH