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TAF4b Regulates Oocyte-Specific Genes Essential for Meiosis.

Grive KJ, Gustafson EA, Seymour KA, Baddoo M, Schorl C, Golnoski K, Rajkovic A, Brodsky AS, Freiman RN - PLoS Genet. (2016)

Bottom Line: To further explore the potential mechanism of TAF4b in promoting ovarian follicle development, we analyzed global gene expression at multiple time points in the human fetal ovary.This computational analysis revealed coordinate expression of human TAF4B and critical regulators and effectors of meiosis I including SYCP3, YBX2, STAG3, and DAZL.Accordingly, TAF4b occupies the proximal promoters of many essential meiosis and oogenesis regulators, including Stra8, Dazl, Figla, and Nobox, and is required for their proper expression.

View Article: PubMed Central - PubMed

Affiliation: MCB Graduate Program, Brown University, Providence, Rhode Island, United States of America.

ABSTRACT
TAF4b is a gonadal-enriched subunit of the general transcription factor TFIID that is implicated in promoting healthy ovarian aging and female fertility in mice and humans. To further explore the potential mechanism of TAF4b in promoting ovarian follicle development, we analyzed global gene expression at multiple time points in the human fetal ovary. This computational analysis revealed coordinate expression of human TAF4B and critical regulators and effectors of meiosis I including SYCP3, YBX2, STAG3, and DAZL. To address the functional relevance of this analysis, we turned to the embryonic Taf4b-deficient mouse ovary where, for the first time, we demonstrate, severe deficits in prophase I progression as well as asynapsis in Taf4b-deficient oocytes. Accordingly, TAF4b occupies the proximal promoters of many essential meiosis and oogenesis regulators, including Stra8, Dazl, Figla, and Nobox, and is required for their proper expression. These data reveal a novel TAF4b function in regulating a meiotic gene expression program in early mouse oogenesis, and support the existence of a highly conserved TAF4b-dependent gene regulatory network promoting early oocyte development in both mice and women.

No MeSH data available.


Related in: MedlinePlus

Reduced MLH1 meiotic recombination foci on pachytene chromosomes in Taf4b-deficient oocytes.(A) Oocyte meiotic chromosome spreads were prepared from E18.5 wild-type and Taf4b-deficient ovaries, and stained with primary antibodies against SYCP3 and MLH1. While wild-type oocytes have one or two intensely-stained MLH1 foci per homologous pair (white solid arrows), few of these foci are evident in Taf4b-deficient oocytes. Instead, the majority of MLH1 foci visible in Taf4b-deficient oocytes are comparatively faint (white dashed arrows) (B) Quantification of average MLH1 foci per oocyte. Taf4b-deficient oocytes possess significantly fewer total MLH1 foci than wild-type oocytes. *: n = 3 animals with 25 or more pachytene oocytes each, one-tailed t-test, p<0.0001
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pgen.1006128.g004: Reduced MLH1 meiotic recombination foci on pachytene chromosomes in Taf4b-deficient oocytes.(A) Oocyte meiotic chromosome spreads were prepared from E18.5 wild-type and Taf4b-deficient ovaries, and stained with primary antibodies against SYCP3 and MLH1. While wild-type oocytes have one or two intensely-stained MLH1 foci per homologous pair (white solid arrows), few of these foci are evident in Taf4b-deficient oocytes. Instead, the majority of MLH1 foci visible in Taf4b-deficient oocytes are comparatively faint (white dashed arrows) (B) Quantification of average MLH1 foci per oocyte. Taf4b-deficient oocytes possess significantly fewer total MLH1 foci than wild-type oocytes. *: n = 3 animals with 25 or more pachytene oocytes each, one-tailed t-test, p<0.0001

Mentions: Finally, as proper synapsis is known to initiate at sites of recombination, the fidelity of meiotic recombination was tested by visualizing MLH1 foci on pachytene chromosomes. While wild-type oocytes possess one or two strongly-stained foci per homologous pair, Taf4b-deficient oocytes lack many of these sites as well as an overall decreased intensity of staining (Fig 4A). Quantification revealed a significant reduction of overall number of MLH1 foci on chromosomes from Taf4b-deficient oocytes (p<0.0001) (Fig 4B). Wild-type oocytes average about 23 foci per cell, while Taf4b-deficient oocytes average about 8 foci per cell with increased variability including many oocytes with no quantifiable foci. Given the loss of Taf4b-deficient oocytes just days after these phenotypes are observed, the data suggest a TAF4b-dependent link between the ability to correctly progress and arrest in prophase I during embryogenesis and postnatal oocyte survival.


TAF4b Regulates Oocyte-Specific Genes Essential for Meiosis.

Grive KJ, Gustafson EA, Seymour KA, Baddoo M, Schorl C, Golnoski K, Rajkovic A, Brodsky AS, Freiman RN - PLoS Genet. (2016)

Reduced MLH1 meiotic recombination foci on pachytene chromosomes in Taf4b-deficient oocytes.(A) Oocyte meiotic chromosome spreads were prepared from E18.5 wild-type and Taf4b-deficient ovaries, and stained with primary antibodies against SYCP3 and MLH1. While wild-type oocytes have one or two intensely-stained MLH1 foci per homologous pair (white solid arrows), few of these foci are evident in Taf4b-deficient oocytes. Instead, the majority of MLH1 foci visible in Taf4b-deficient oocytes are comparatively faint (white dashed arrows) (B) Quantification of average MLH1 foci per oocyte. Taf4b-deficient oocytes possess significantly fewer total MLH1 foci than wild-type oocytes. *: n = 3 animals with 25 or more pachytene oocytes each, one-tailed t-test, p<0.0001
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4920394&req=5

pgen.1006128.g004: Reduced MLH1 meiotic recombination foci on pachytene chromosomes in Taf4b-deficient oocytes.(A) Oocyte meiotic chromosome spreads were prepared from E18.5 wild-type and Taf4b-deficient ovaries, and stained with primary antibodies against SYCP3 and MLH1. While wild-type oocytes have one or two intensely-stained MLH1 foci per homologous pair (white solid arrows), few of these foci are evident in Taf4b-deficient oocytes. Instead, the majority of MLH1 foci visible in Taf4b-deficient oocytes are comparatively faint (white dashed arrows) (B) Quantification of average MLH1 foci per oocyte. Taf4b-deficient oocytes possess significantly fewer total MLH1 foci than wild-type oocytes. *: n = 3 animals with 25 or more pachytene oocytes each, one-tailed t-test, p<0.0001
Mentions: Finally, as proper synapsis is known to initiate at sites of recombination, the fidelity of meiotic recombination was tested by visualizing MLH1 foci on pachytene chromosomes. While wild-type oocytes possess one or two strongly-stained foci per homologous pair, Taf4b-deficient oocytes lack many of these sites as well as an overall decreased intensity of staining (Fig 4A). Quantification revealed a significant reduction of overall number of MLH1 foci on chromosomes from Taf4b-deficient oocytes (p<0.0001) (Fig 4B). Wild-type oocytes average about 23 foci per cell, while Taf4b-deficient oocytes average about 8 foci per cell with increased variability including many oocytes with no quantifiable foci. Given the loss of Taf4b-deficient oocytes just days after these phenotypes are observed, the data suggest a TAF4b-dependent link between the ability to correctly progress and arrest in prophase I during embryogenesis and postnatal oocyte survival.

Bottom Line: To further explore the potential mechanism of TAF4b in promoting ovarian follicle development, we analyzed global gene expression at multiple time points in the human fetal ovary.This computational analysis revealed coordinate expression of human TAF4B and critical regulators and effectors of meiosis I including SYCP3, YBX2, STAG3, and DAZL.Accordingly, TAF4b occupies the proximal promoters of many essential meiosis and oogenesis regulators, including Stra8, Dazl, Figla, and Nobox, and is required for their proper expression.

View Article: PubMed Central - PubMed

Affiliation: MCB Graduate Program, Brown University, Providence, Rhode Island, United States of America.

ABSTRACT
TAF4b is a gonadal-enriched subunit of the general transcription factor TFIID that is implicated in promoting healthy ovarian aging and female fertility in mice and humans. To further explore the potential mechanism of TAF4b in promoting ovarian follicle development, we analyzed global gene expression at multiple time points in the human fetal ovary. This computational analysis revealed coordinate expression of human TAF4B and critical regulators and effectors of meiosis I including SYCP3, YBX2, STAG3, and DAZL. To address the functional relevance of this analysis, we turned to the embryonic Taf4b-deficient mouse ovary where, for the first time, we demonstrate, severe deficits in prophase I progression as well as asynapsis in Taf4b-deficient oocytes. Accordingly, TAF4b occupies the proximal promoters of many essential meiosis and oogenesis regulators, including Stra8, Dazl, Figla, and Nobox, and is required for their proper expression. These data reveal a novel TAF4b function in regulating a meiotic gene expression program in early mouse oogenesis, and support the existence of a highly conserved TAF4b-dependent gene regulatory network promoting early oocyte development in both mice and women.

No MeSH data available.


Related in: MedlinePlus