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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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X-linked and the autosomal testis-biased genes show similar patterns of activation in testis development. (A) X-linked genes; the profile for the known spermatocyte-specific gene Sdic is outlined as a black dotted line. Other genes are CG15450, CG1314, CG1338, CG15711, CG15452, CG11227 and CG1324 (gray lines). (B) autosomal genes; the profiles for the known spermatocyte-specific genes fzo, dj, and β(2)Tubulin are outlined as black dotted lines. The profile for the gene ocn which is the source of promoter in the transgene based study of Hense et al. [15] is outlined as a black solid line. Other genes are CG6262, CG3483, CG7813, CG3492, CG15874, CG3494, CG16837, CG4439, CG4750, CG15873, CG15925, CG7848, CG15710, Eyc, Mst35Ba, and Mst35Bb (gray lines). (C) Box plot analysis of gene expression data (A, B) shows no significant differences in the expression patterns between the X-linked (orange) and the autosomal (blue) gene sets. For each gene, expression level in pupae served as the reference.
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Figure 1: X-linked and the autosomal testis-biased genes show similar patterns of activation in testis development. (A) X-linked genes; the profile for the known spermatocyte-specific gene Sdic is outlined as a black dotted line. Other genes are CG15450, CG1314, CG1338, CG15711, CG15452, CG11227 and CG1324 (gray lines). (B) autosomal genes; the profiles for the known spermatocyte-specific genes fzo, dj, and β(2)Tubulin are outlined as black dotted lines. The profile for the gene ocn which is the source of promoter in the transgene based study of Hense et al. [15] is outlined as a black solid line. Other genes are CG6262, CG3483, CG7813, CG3492, CG15874, CG3494, CG16837, CG4439, CG4750, CG15873, CG15925, CG7848, CG15710, Eyc, Mst35Ba, and Mst35Bb (gray lines). (C) Box plot analysis of gene expression data (A, B) shows no significant differences in the expression patterns between the X-linked (orange) and the autosomal (blue) gene sets. For each gene, expression level in pupae served as the reference.

Mentions: Testes were collected daily from day four (second instar) through day seven (Figure 1, dL), at which point third-instar larvae started to pupate (Figure 1, dP). Since the first wave of germline differentiation reaches meiotic divisions approximately at the onset of pupation [19] and spermatocytes become the predominant cell type in testes of third instar larvae [26], this analysis traced changes in gene expression associated with the accumulation and maturation of spermatocytes. Accordingly, transcripts of known spermatocyte-specific genes, both autosomal and X-linked, showed a steady increase throughout testis development in our series of samples (dotted lines on Figure 1A, B). Other analyzed genes, including those located on the X chromosome, showed the same pattern indicating that their activation occurs in the meiotic germline. The pooled data also show a striking similarity of the expression patterns between the groups of X-linked and autosomal genes (Figure 1C). We further sought to determine whether the relatively small selection of X-linked genes for our study could have influenced our conclusion that these genes are usually activated concomitant with meiosis. To assess a larger sample, we analyzed published in situ hybridization data for 501 X-linked genes [21] and found that 474 of them (94%) are induced in primary spermatocytes. Cumulatively, the above data obtained by different approaches convincingly show that numerous X-linked genes are activated in the male meiotic germline. It is not clear then why the transgenes driven by promoter of the testis-specific ocn gene could not show efficient expression when integrated into the X chromosome [16], given that ocn shows the same expression profile as endogenous X-linked testis-biased genes (compare the solid line on Figure 1B for ocn to the profiles in Figure 1A). However, regardless of the mechanism(s) of silencing, the ocn transgenes [16] do not appear representative of the X-linked genes that are commonly expressed in spermatocytes.


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)

X-linked and the autosomal testis-biased genes show similar patterns of activation in testis development. (A) X-linked genes; the profile for the known spermatocyte-specific gene Sdic is outlined as a black dotted line. Other genes are CG15450, CG1314, CG1338, CG15711, CG15452, CG11227 and CG1324 (gray lines). (B) autosomal genes; the profiles for the known spermatocyte-specific genes fzo, dj, and β(2)Tubulin are outlined as black dotted lines. The profile for the gene ocn which is the source of promoter in the transgene based study of Hense et al. [15] is outlined as a black solid line. Other genes are CG6262, CG3483, CG7813, CG3492, CG15874, CG3494, CG16837, CG4439, CG4750, CG15873, CG15925, CG7848, CG15710, Eyc, Mst35Ba, and Mst35Bb (gray lines). (C) Box plot analysis of gene expression data (A, B) shows no significant differences in the expression patterns between the X-linked (orange) and the autosomal (blue) gene sets. For each gene, expression level in pupae served as the reference.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: X-linked and the autosomal testis-biased genes show similar patterns of activation in testis development. (A) X-linked genes; the profile for the known spermatocyte-specific gene Sdic is outlined as a black dotted line. Other genes are CG15450, CG1314, CG1338, CG15711, CG15452, CG11227 and CG1324 (gray lines). (B) autosomal genes; the profiles for the known spermatocyte-specific genes fzo, dj, and β(2)Tubulin are outlined as black dotted lines. The profile for the gene ocn which is the source of promoter in the transgene based study of Hense et al. [15] is outlined as a black solid line. Other genes are CG6262, CG3483, CG7813, CG3492, CG15874, CG3494, CG16837, CG4439, CG4750, CG15873, CG15925, CG7848, CG15710, Eyc, Mst35Ba, and Mst35Bb (gray lines). (C) Box plot analysis of gene expression data (A, B) shows no significant differences in the expression patterns between the X-linked (orange) and the autosomal (blue) gene sets. For each gene, expression level in pupae served as the reference.
Mentions: Testes were collected daily from day four (second instar) through day seven (Figure 1, dL), at which point third-instar larvae started to pupate (Figure 1, dP). Since the first wave of germline differentiation reaches meiotic divisions approximately at the onset of pupation [19] and spermatocytes become the predominant cell type in testes of third instar larvae [26], this analysis traced changes in gene expression associated with the accumulation and maturation of spermatocytes. Accordingly, transcripts of known spermatocyte-specific genes, both autosomal and X-linked, showed a steady increase throughout testis development in our series of samples (dotted lines on Figure 1A, B). Other analyzed genes, including those located on the X chromosome, showed the same pattern indicating that their activation occurs in the meiotic germline. The pooled data also show a striking similarity of the expression patterns between the groups of X-linked and autosomal genes (Figure 1C). We further sought to determine whether the relatively small selection of X-linked genes for our study could have influenced our conclusion that these genes are usually activated concomitant with meiosis. To assess a larger sample, we analyzed published in situ hybridization data for 501 X-linked genes [21] and found that 474 of them (94%) are induced in primary spermatocytes. Cumulatively, the above data obtained by different approaches convincingly show that numerous X-linked genes are activated in the male meiotic germline. It is not clear then why the transgenes driven by promoter of the testis-specific ocn gene could not show efficient expression when integrated into the X chromosome [16], given that ocn shows the same expression profile as endogenous X-linked testis-biased genes (compare the solid line on Figure 1B for ocn to the profiles in Figure 1A). However, regardless of the mechanism(s) of silencing, the ocn transgenes [16] do not appear representative of the X-linked genes that are commonly expressed in spermatocytes.

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