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Conservation analysis of sequences flanking the testis-determining gene Sry in 17 mammalian species.

Larney C, Bailey TL, Koopman P - BMC Dev. Biol. (2015)

Bottom Line: We identified position-specific conservation of binding motifs for multiple transcription factor families, including GATA binding factors and Oct/Sox dimers.In contrast with the landscape of extremely low sequence conservation around the Sry coding region, our analysis highlighted a strongly conserved interval of ~106 bp within the Sry promoter (which we term the Sry Proximal Conserved Interval, SPCI).The unusually fast pace of sequence drift on the Y chromosome sharpens the likely functional significance of both the SPCI and the identified binding motifs, providing a basis for future studies of the role(s) of these elements in Sry regulation.

View Article: PubMed Central - PubMed

Affiliation: Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, 4072, Australia.

ABSTRACT

Background: Sex determination in mammals requires expression of the Y-linked gene Sry in the bipotential genital ridges of the XY embryo. Even minor delay of the onset of Sry expression can result in XY sex reversal, highlighting the need for accurate gene regulation during sex determination. However, the location of critical regulatory elements remains unknown. Here, we analysed Sry flanking sequences across many species, using newly available genome sequences and computational tools, to better understand Sry's genomic context and to identify conserved regions predictive of functional roles.

Methods: Flanking sequences from 17 species were analysed using both global and local sequence alignment methods. Multiple motif searches were employed to characterise common motifs in otherwise unconserved sequence.

Results: We identified position-specific conservation of binding motifs for multiple transcription factor families, including GATA binding factors and Oct/Sox dimers. In contrast with the landscape of extremely low sequence conservation around the Sry coding region, our analysis highlighted a strongly conserved interval of ~106 bp within the Sry promoter (which we term the Sry Proximal Conserved Interval, SPCI). We further report that inverted repeats flanking murine Sry are much larger than previously recognised.

Conclusions: The unusually fast pace of sequence drift on the Y chromosome sharpens the likely functional significance of both the SPCI and the identified binding motifs, providing a basis for future studies of the role(s) of these elements in Sry regulation.

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Related in: MedlinePlus

Just two short conserved regions are present in the 10 kb 5’ of Sry in human and mouse. Plots of the probability of conservation in the 10 kb region upstream of the start of translation of the Sry gene in (a) human and (b) mouse. Conservation is estimated by RPhast from a multiple alignment generated by MUSCLE using repeat-masked flanking sequences of 17 species
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Fig4: Just two short conserved regions are present in the 10 kb 5’ of Sry in human and mouse. Plots of the probability of conservation in the 10 kb region upstream of the start of translation of the Sry gene in (a) human and (b) mouse. Conservation is estimated by RPhast from a multiple alignment generated by MUSCLE using repeat-masked flanking sequences of 17 species

Mentions: To quantify the level of conservation in the flanking regions, we took 10 kb sequences from immediately 5’ of the Sry start codon in 17 species, masked known repeats using RepeatMasker [20], and then aligned the sequences using MUSCLE [16] (Additional file 2). Estimating the probability of conservation at each position of the resulting alignment with RPhast [17] (Fig. 4), we observed in both human and mouse two closely spaced conserved regions just a few hundred base pairs 5’ of the ORF (Fig. 4, insets). A similar analysis of 10 kb flanking sequences from 3’ of the gene (Additional file 3) found only two short, incompletely conserved regions (results not shown).Fig. 4


Conservation analysis of sequences flanking the testis-determining gene Sry in 17 mammalian species.

Larney C, Bailey TL, Koopman P - BMC Dev. Biol. (2015)

Just two short conserved regions are present in the 10 kb 5’ of Sry in human and mouse. Plots of the probability of conservation in the 10 kb region upstream of the start of translation of the Sry gene in (a) human and (b) mouse. Conservation is estimated by RPhast from a multiple alignment generated by MUSCLE using repeat-masked flanking sequences of 17 species
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4595323&req=5

Fig4: Just two short conserved regions are present in the 10 kb 5’ of Sry in human and mouse. Plots of the probability of conservation in the 10 kb region upstream of the start of translation of the Sry gene in (a) human and (b) mouse. Conservation is estimated by RPhast from a multiple alignment generated by MUSCLE using repeat-masked flanking sequences of 17 species
Mentions: To quantify the level of conservation in the flanking regions, we took 10 kb sequences from immediately 5’ of the Sry start codon in 17 species, masked known repeats using RepeatMasker [20], and then aligned the sequences using MUSCLE [16] (Additional file 2). Estimating the probability of conservation at each position of the resulting alignment with RPhast [17] (Fig. 4), we observed in both human and mouse two closely spaced conserved regions just a few hundred base pairs 5’ of the ORF (Fig. 4, insets). A similar analysis of 10 kb flanking sequences from 3’ of the gene (Additional file 3) found only two short, incompletely conserved regions (results not shown).Fig. 4

Bottom Line: We identified position-specific conservation of binding motifs for multiple transcription factor families, including GATA binding factors and Oct/Sox dimers.In contrast with the landscape of extremely low sequence conservation around the Sry coding region, our analysis highlighted a strongly conserved interval of ~106 bp within the Sry promoter (which we term the Sry Proximal Conserved Interval, SPCI).The unusually fast pace of sequence drift on the Y chromosome sharpens the likely functional significance of both the SPCI and the identified binding motifs, providing a basis for future studies of the role(s) of these elements in Sry regulation.

View Article: PubMed Central - PubMed

Affiliation: Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, 4072, Australia.

ABSTRACT

Background: Sex determination in mammals requires expression of the Y-linked gene Sry in the bipotential genital ridges of the XY embryo. Even minor delay of the onset of Sry expression can result in XY sex reversal, highlighting the need for accurate gene regulation during sex determination. However, the location of critical regulatory elements remains unknown. Here, we analysed Sry flanking sequences across many species, using newly available genome sequences and computational tools, to better understand Sry's genomic context and to identify conserved regions predictive of functional roles.

Methods: Flanking sequences from 17 species were analysed using both global and local sequence alignment methods. Multiple motif searches were employed to characterise common motifs in otherwise unconserved sequence.

Results: We identified position-specific conservation of binding motifs for multiple transcription factor families, including GATA binding factors and Oct/Sox dimers. In contrast with the landscape of extremely low sequence conservation around the Sry coding region, our analysis highlighted a strongly conserved interval of ~106 bp within the Sry promoter (which we term the Sry Proximal Conserved Interval, SPCI). We further report that inverted repeats flanking murine Sry are much larger than previously recognised.

Conclusions: The unusually fast pace of sequence drift on the Y chromosome sharpens the likely functional significance of both the SPCI and the identified binding motifs, providing a basis for future studies of the role(s) of these elements in Sry regulation.

Show MeSH
Related in: MedlinePlus