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Lack of global meiotic sex chromosome inactivation, and paucity of tissue-specific gene expression on the Drosophila X chromosome.

Mikhaylova LM, Nurminsky DI - BMC Biol. (2011)

Bottom Line: Bioinformatics analysis shows that while tissue-specific genes often bind silencing-associated factors in embryonic and cultured cells, this trend is less prominent for the X-linked genes.Our data show that the global meiotic inactivation of the X chromosome does not occur in Drosophila.This effect, probably caused by dosage compensation counteracting repression of the X-linked genes, may be the cause of the exodus of highly tissue-biased genes to the autosomes.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Anatomy and Cellular Biology, Tufts University School of Medicine, Boston, USA.

ABSTRACT

Background: Paucity of male-biased genes on the Drosophila X chromosome is a well-established phenomenon, thought to be specifically linked to the role of these genes in reproduction and/or their expression in the meiotic male germline. In particular, meiotic sex chromosome inactivation (MSCI) has been widely considered a driving force behind depletion of spermatocyte-biased X-linked genes in Drosophila by analogy with mammals, even though the existence of global MCSI in Drosophila has not been proven.

Results: Microarray-based study and qRT-PCR analyses show that the dynamics of gene expression during testis development are very similar between X-linked and autosomal genes, with both showing transcriptional activation concomitant with meiosis. However, the genes showing at least ten-fold expression bias toward testis are significantly underrepresented on the X chromosome. Intriguingly, the genes with similar expression bias toward tissues other than testis, even those not apparently associated with reproduction, are also strongly underrepresented on the X. Bioinformatics analysis shows that while tissue-specific genes often bind silencing-associated factors in embryonic and cultured cells, this trend is less prominent for the X-linked genes.

Conclusions: Our data show that the global meiotic inactivation of the X chromosome does not occur in Drosophila. Paucity of testis-biased genes on the X appears not to be linked to reproduction or germline-specific events, but rather reflects a general underrepresentation of tissue-biased genes on this chromosome. Our analyses suggest that the activation/repression switch mechanisms that probably orchestrate the highly-biased expression of tissue-specific genes are generally not efficient on the X chromosome. This effect, probably caused by dosage compensation counteracting repression of the X-linked genes, may be the cause of the exodus of highly tissue-biased genes to the autosomes.

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'Inversed' correlations between gene regulation in testis development and chromatin modifications in somatic cells. For each of the developmental time points indicated on the horizontal axis, correlations were calculated between up-regulation of genes in testis relative to the earliest time point (from microarray data) and binding of the same genes to the shown chromatin proteins in embryos or somatic cells [29,30]. Yellow, orange, and purple colors represent proteins that are generally associated with gene silencing, and blue and green colors represent proteins generally associated with active gene expression.
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Figure 5: 'Inversed' correlations between gene regulation in testis development and chromatin modifications in somatic cells. For each of the developmental time points indicated on the horizontal axis, correlations were calculated between up-regulation of genes in testis relative to the earliest time point (from microarray data) and binding of the same genes to the shown chromatin proteins in embryos or somatic cells [29,30]. Yellow, orange, and purple colors represent proteins that are generally associated with gene silencing, and blue and green colors represent proteins generally associated with active gene expression.

Mentions: Based on our analyses, we suggest that the X chromosome provides an inferior environment for specialized genes with expression highly biased toward particular differentiated cell types. To gain a better understanding of the underlying mechanisms, we analyzed the binding of diverse chromatin proteins to the X-linked and autosomal tissue-biased genes. First, we analyzed the correlations between gene expression in testis development and binding of 27 chromatin proteins in embryonic and cultured cells. Changes in gene expression were measured as signal fold changes for every time point in our microarray-based analysis; the earliest analyzed stage (four-day old larvae) served as the reference. Chromatin protein binding was assessed as the fold enrichment in chromatin immunoprecipitation or in DNA adenine methyltransferase identification experiments [30,31]. We have found a correlation that was 'inversed' with respect to the major roles of the analyzed proteins: that is, gene up-regulation in testis development was positively correlated with the binding of silencing-associated proteins in embryos and cultured cells (Figure 5, results for proteins with insignificant correlations are not shown). Specifically, testis-up-regulated genes showed prominent associations with histone H1, histone H3 trimethylated at K27, LamDmo, D1, and Polycomb (Pc) and Pc group proteins esc and Sce [25,32-38]. In addition, a negative correlation was apparent between genes up-regulated in testis and the binding of gene activation-associated proteins in embryos and cultured cells (these proteins include histone variant H3.3A, H3 trimethylated at K4, DJun, and bcd) [39-41]. These observations imply that testis-biased expression is regulated by a two-prong 'switch' mechanism comprised of gene activation in testis (most likely, male germline) and gene repression in other tissues and cell types.


Lack of global meiotic sex chromosome inactivation, and paucity of tissue-specific gene expression on the Drosophila X chromosome.

Mikhaylova LM, Nurminsky DI - BMC Biol. (2011)

'Inversed' correlations between gene regulation in testis development and chromatin modifications in somatic cells. For each of the developmental time points indicated on the horizontal axis, correlations were calculated between up-regulation of genes in testis relative to the earliest time point (from microarray data) and binding of the same genes to the shown chromatin proteins in embryos or somatic cells [29,30]. Yellow, orange, and purple colors represent proteins that are generally associated with gene silencing, and blue and green colors represent proteins generally associated with active gene expression.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3104377&req=5

Figure 5: 'Inversed' correlations between gene regulation in testis development and chromatin modifications in somatic cells. For each of the developmental time points indicated on the horizontal axis, correlations were calculated between up-regulation of genes in testis relative to the earliest time point (from microarray data) and binding of the same genes to the shown chromatin proteins in embryos or somatic cells [29,30]. Yellow, orange, and purple colors represent proteins that are generally associated with gene silencing, and blue and green colors represent proteins generally associated with active gene expression.
Mentions: Based on our analyses, we suggest that the X chromosome provides an inferior environment for specialized genes with expression highly biased toward particular differentiated cell types. To gain a better understanding of the underlying mechanisms, we analyzed the binding of diverse chromatin proteins to the X-linked and autosomal tissue-biased genes. First, we analyzed the correlations between gene expression in testis development and binding of 27 chromatin proteins in embryonic and cultured cells. Changes in gene expression were measured as signal fold changes for every time point in our microarray-based analysis; the earliest analyzed stage (four-day old larvae) served as the reference. Chromatin protein binding was assessed as the fold enrichment in chromatin immunoprecipitation or in DNA adenine methyltransferase identification experiments [30,31]. We have found a correlation that was 'inversed' with respect to the major roles of the analyzed proteins: that is, gene up-regulation in testis development was positively correlated with the binding of silencing-associated proteins in embryos and cultured cells (Figure 5, results for proteins with insignificant correlations are not shown). Specifically, testis-up-regulated genes showed prominent associations with histone H1, histone H3 trimethylated at K27, LamDmo, D1, and Polycomb (Pc) and Pc group proteins esc and Sce [25,32-38]. In addition, a negative correlation was apparent between genes up-regulated in testis and the binding of gene activation-associated proteins in embryos and cultured cells (these proteins include histone variant H3.3A, H3 trimethylated at K4, DJun, and bcd) [39-41]. These observations imply that testis-biased expression is regulated by a two-prong 'switch' mechanism comprised of gene activation in testis (most likely, male germline) and gene repression in other tissues and cell types.

Bottom Line: Bioinformatics analysis shows that while tissue-specific genes often bind silencing-associated factors in embryonic and cultured cells, this trend is less prominent for the X-linked genes.Our data show that the global meiotic inactivation of the X chromosome does not occur in Drosophila.This effect, probably caused by dosage compensation counteracting repression of the X-linked genes, may be the cause of the exodus of highly tissue-biased genes to the autosomes.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Anatomy and Cellular Biology, Tufts University School of Medicine, Boston, USA.

ABSTRACT

Background: Paucity of male-biased genes on the Drosophila X chromosome is a well-established phenomenon, thought to be specifically linked to the role of these genes in reproduction and/or their expression in the meiotic male germline. In particular, meiotic sex chromosome inactivation (MSCI) has been widely considered a driving force behind depletion of spermatocyte-biased X-linked genes in Drosophila by analogy with mammals, even though the existence of global MCSI in Drosophila has not been proven.

Results: Microarray-based study and qRT-PCR analyses show that the dynamics of gene expression during testis development are very similar between X-linked and autosomal genes, with both showing transcriptional activation concomitant with meiosis. However, the genes showing at least ten-fold expression bias toward testis are significantly underrepresented on the X chromosome. Intriguingly, the genes with similar expression bias toward tissues other than testis, even those not apparently associated with reproduction, are also strongly underrepresented on the X. Bioinformatics analysis shows that while tissue-specific genes often bind silencing-associated factors in embryonic and cultured cells, this trend is less prominent for the X-linked genes.

Conclusions: Our data show that the global meiotic inactivation of the X chromosome does not occur in Drosophila. Paucity of testis-biased genes on the X appears not to be linked to reproduction or germline-specific events, but rather reflects a general underrepresentation of tissue-biased genes on this chromosome. Our analyses suggest that the activation/repression switch mechanisms that probably orchestrate the highly-biased expression of tissue-specific genes are generally not efficient on the X chromosome. This effect, probably caused by dosage compensation counteracting repression of the X-linked genes, may be the cause of the exodus of highly tissue-biased genes to the autosomes.

Show MeSH
Related in: MedlinePlus