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X-to-autosome expression and msl-2 transcript abundance correlate among Drosophila melanogaster somatic tissues.

Vensko Ii SP, Stone EA - PeerJ (2015)

Bottom Line: Recent advances in high-throughput technologies have improved our understanding of how the MSL complex mediates dosage compensation through chromosome-wide chromatin modifications.Specifically, we find X-to-autosome expression correlates with the tissue-specific expression of msl-2 which encodes an essential male-specific component of the MSL complex.Furthermore, this result has consequences for models explaining the organismal-scale molecular and evolutionary consequences of MSL-mediated dosage compensation.

View Article: PubMed Central - HTML - PubMed

Affiliation: Program in Genetics, North Carolina State University , Raleigh, NC , USA.

ABSTRACT
In Drosophila melanogaster, the male-specific lethal (MSL) complex has been studied extensively for its role in upregulating male X-linked genes. Recent advances in high-throughput technologies have improved our understanding of how the MSL complex mediates dosage compensation through chromosome-wide chromatin modifications. Most studies, however, have focused on cell line models that cannot reflect any potential heterogeneity of in vivo dosage compensation. Comparisons between cell line and organismal gene-level dosage compensation upregulation suggest the possibility of variation in MSL complex activity among somatic tissues. We hypothesize the degree, up to but not exceeding 2-fold, to which the MSL complex upregulates male X-linked genes varies quantitatively by tissue type. In this model, MSL complex abundance acts as a rheostat to control the extent of upregulation. Using publicly available expression data, we provide evidence for our model in Drosophila somatic tissues. Specifically, we find X-to-autosome expression correlates with the tissue-specific expression of msl-2 which encodes an essential male-specific component of the MSL complex. This result suggests MSL complex mediated dosage compensation varies quantitatively by tissue type. Furthermore, this result has consequences for models explaining the organismal-scale molecular and evolutionary consequences of MSL-mediated dosage compensation.

No MeSH data available.


Related in: MedlinePlus

X-to-autosome expression variation among somatic tissues.X-to-autosome expression estimates were calculated for all four FlyAtlas replicates for each tissue using the log2 transformed ratios of the mean expression of X-linked expressed genes to mean expression of autosomal expressed genes for both the (A) non-sex-biased gene set and (B) sex-biased gene set. Tissues are sorted by their median log2 ratio among the FlyAtlas replicates.
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fig-1: X-to-autosome expression variation among somatic tissues.X-to-autosome expression estimates were calculated for all four FlyAtlas replicates for each tissue using the log2 transformed ratios of the mean expression of X-linked expressed genes to mean expression of autosomal expressed genes for both the (A) non-sex-biased gene set and (B) sex-biased gene set. Tissues are sorted by their median log2 ratio among the FlyAtlas replicates.

Mentions: There is ample evidence that the expression patterns of X-linked genes vary in their tissue distribution (Chintapalli, Wang & Dow, 2007). For these genes to exhibit varying levels of dosage compensation on an organismal level, dosage compensation must also be differentially active across the male somatic tissues in which these genes are expressed. Noting that the primary role of the MSL complex in dosage compensation is to offset male monosomy by upregulating a majority of X-linked genes, it stands to reason that decreased complex activity should associate with a larger difference in expression levels between the X and the autosomes. If the degree of difference varies quantitatively across tissues, this would provide evidence consistent with an analog model of tissue-specific dosage compensation. While this approach appears straight-forward, one must be cognizant of the differing evolutionary histories of the X chromosome and autosomes that may dilute any signal of X chromosome dosage compensation upregulation. Taking this into consideration, we partitioned genes into a non-sex-biased set and a sex-biased set. We expect the non-sex-biased gene set to be dosage compensated, show similar enrichment on the X chromosome and autosomes, and be less likely to be regulated sex-specific mechanisms. We expect the sex-biased gene set, on the other hand, to be likely experiencing some level of dosage compensation but for this signal to be diluted by sex-specific regulatory mechanisms and an unequal distribution between the X chromosome and autosomes. These two gene sets, therefore, provide us the ability to detect any signal of dosage compensation in the non-sex-biased gene set while ensuring sex-specific mechanisms and differing gene content between the X chromosome and autosomes are not driving the signal. We tested for variation in X-to-autosome expression among tissues for both gene sets by calculating the difference between mean X chromosome gene expression and mean autosome gene expression. We found significant variation in X-to-autosome expression among somatic adult tissues for both the non-biased gene set (Fig. 1A, F15,48 ≈ 9.40, p < 0.005) and sex-biased gene set (Fig. 1B, F15,48 ≈ 13.64, p < 0.005). These trends were also observed among non-sex-biased genes within larval tissues (Fig. S1, F7,24 ≈ 279.52, p < 0.005). In line with our expectations, the adult testis shows the lowest X-to-autosome expression among adult tissues (see Fig. S2). Interestingly, there is no significant correlation between the non-sex-biased gene set and sex-biased gene set which suggests they are under differing transcriptional regulatory regimes. While these results hint toward the possibility of variation in dosage compensation activity among somatic tissues, other mechanisms may instead be responsible. We sought further evidence of our hypothesis by interrogating tissue-specific variation of the MSL complex itself.


X-to-autosome expression and msl-2 transcript abundance correlate among Drosophila melanogaster somatic tissues.

Vensko Ii SP, Stone EA - PeerJ (2015)

X-to-autosome expression variation among somatic tissues.X-to-autosome expression estimates were calculated for all four FlyAtlas replicates for each tissue using the log2 transformed ratios of the mean expression of X-linked expressed genes to mean expression of autosomal expressed genes for both the (A) non-sex-biased gene set and (B) sex-biased gene set. Tissues are sorted by their median log2 ratio among the FlyAtlas replicates.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4338770&req=5

fig-1: X-to-autosome expression variation among somatic tissues.X-to-autosome expression estimates were calculated for all four FlyAtlas replicates for each tissue using the log2 transformed ratios of the mean expression of X-linked expressed genes to mean expression of autosomal expressed genes for both the (A) non-sex-biased gene set and (B) sex-biased gene set. Tissues are sorted by their median log2 ratio among the FlyAtlas replicates.
Mentions: There is ample evidence that the expression patterns of X-linked genes vary in their tissue distribution (Chintapalli, Wang & Dow, 2007). For these genes to exhibit varying levels of dosage compensation on an organismal level, dosage compensation must also be differentially active across the male somatic tissues in which these genes are expressed. Noting that the primary role of the MSL complex in dosage compensation is to offset male monosomy by upregulating a majority of X-linked genes, it stands to reason that decreased complex activity should associate with a larger difference in expression levels between the X and the autosomes. If the degree of difference varies quantitatively across tissues, this would provide evidence consistent with an analog model of tissue-specific dosage compensation. While this approach appears straight-forward, one must be cognizant of the differing evolutionary histories of the X chromosome and autosomes that may dilute any signal of X chromosome dosage compensation upregulation. Taking this into consideration, we partitioned genes into a non-sex-biased set and a sex-biased set. We expect the non-sex-biased gene set to be dosage compensated, show similar enrichment on the X chromosome and autosomes, and be less likely to be regulated sex-specific mechanisms. We expect the sex-biased gene set, on the other hand, to be likely experiencing some level of dosage compensation but for this signal to be diluted by sex-specific regulatory mechanisms and an unequal distribution between the X chromosome and autosomes. These two gene sets, therefore, provide us the ability to detect any signal of dosage compensation in the non-sex-biased gene set while ensuring sex-specific mechanisms and differing gene content between the X chromosome and autosomes are not driving the signal. We tested for variation in X-to-autosome expression among tissues for both gene sets by calculating the difference between mean X chromosome gene expression and mean autosome gene expression. We found significant variation in X-to-autosome expression among somatic adult tissues for both the non-biased gene set (Fig. 1A, F15,48 ≈ 9.40, p < 0.005) and sex-biased gene set (Fig. 1B, F15,48 ≈ 13.64, p < 0.005). These trends were also observed among non-sex-biased genes within larval tissues (Fig. S1, F7,24 ≈ 279.52, p < 0.005). In line with our expectations, the adult testis shows the lowest X-to-autosome expression among adult tissues (see Fig. S2). Interestingly, there is no significant correlation between the non-sex-biased gene set and sex-biased gene set which suggests they are under differing transcriptional regulatory regimes. While these results hint toward the possibility of variation in dosage compensation activity among somatic tissues, other mechanisms may instead be responsible. We sought further evidence of our hypothesis by interrogating tissue-specific variation of the MSL complex itself.

Bottom Line: Recent advances in high-throughput technologies have improved our understanding of how the MSL complex mediates dosage compensation through chromosome-wide chromatin modifications.Specifically, we find X-to-autosome expression correlates with the tissue-specific expression of msl-2 which encodes an essential male-specific component of the MSL complex.Furthermore, this result has consequences for models explaining the organismal-scale molecular and evolutionary consequences of MSL-mediated dosage compensation.

View Article: PubMed Central - HTML - PubMed

Affiliation: Program in Genetics, North Carolina State University , Raleigh, NC , USA.

ABSTRACT
In Drosophila melanogaster, the male-specific lethal (MSL) complex has been studied extensively for its role in upregulating male X-linked genes. Recent advances in high-throughput technologies have improved our understanding of how the MSL complex mediates dosage compensation through chromosome-wide chromatin modifications. Most studies, however, have focused on cell line models that cannot reflect any potential heterogeneity of in vivo dosage compensation. Comparisons between cell line and organismal gene-level dosage compensation upregulation suggest the possibility of variation in MSL complex activity among somatic tissues. We hypothesize the degree, up to but not exceeding 2-fold, to which the MSL complex upregulates male X-linked genes varies quantitatively by tissue type. In this model, MSL complex abundance acts as a rheostat to control the extent of upregulation. Using publicly available expression data, we provide evidence for our model in Drosophila somatic tissues. Specifically, we find X-to-autosome expression correlates with the tissue-specific expression of msl-2 which encodes an essential male-specific component of the MSL complex. This result suggests MSL complex mediated dosage compensation varies quantitatively by tissue type. Furthermore, this result has consequences for models explaining the organismal-scale molecular and evolutionary consequences of MSL-mediated dosage compensation.

No MeSH data available.


Related in: MedlinePlus