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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 expression of meiosis genes in E13.5 Taf4b-deficient ovaries: Quantitative RT-PCR was used to compare differential gene expression between E13.5 wild-type and Taf4b-deficient ovary cDNA. RT-PCR was performed in technical triplicate and values were normalized to 18S rRNA with fold-change displayed after setting the wild-type value to 1.n = 4 wild-type animals and 3 Taf4b-deficient animals. Taf4b-deficient oocytes displayed about 25% of the Stra8, Sycp1, and Sycp2 mRNA expression of wild-type oocytes, while the somatic marker Wnt4 is not significantly changed between genotypes. Error bars represent SEM, and p-values were determined by Unpaired Student T-Test (* = p < 0.05; *** = p < 0.005).
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pgen.1006128.g007: Reduced expression of meiosis genes in E13.5 Taf4b-deficient ovaries: Quantitative RT-PCR was used to compare differential gene expression between E13.5 wild-type and Taf4b-deficient ovary cDNA. RT-PCR was performed in technical triplicate and values were normalized to 18S rRNA with fold-change displayed after setting the wild-type value to 1.n = 4 wild-type animals and 3 Taf4b-deficient animals. Taf4b-deficient oocytes displayed about 25% of the Stra8, Sycp1, and Sycp2 mRNA expression of wild-type oocytes, while the somatic marker Wnt4 is not significantly changed between genotypes. Error bars represent SEM, and p-values were determined by Unpaired Student T-Test (* = p < 0.05; *** = p < 0.005).

Mentions: To better understand if meiotic onset may also be affected in Taf4b-deficient oocytes, mRNA expression of Stra8 was tested at E13.5, the developmental time at which it is first activated by RA [3]. Notably, Stra8 expression in Taf4b-deficient ovaries is approximately 25% of that expressed in wild-type ovaries at the same time (Fig 7). Genes downstream of Stra8, including Sycp1 and Sycp2, exhibit similar reduced expression, suggesting that TAF4b may be important for meiotic onset as well as progression through direct transcriptional modulation of Stra8. In contrast to these oocyte-specific genes, Wnt4 expression [36] is not significantly changed in Taf4b-deficient ovaries at this time, suggesting that TAF4b is specifically promoting oocyte-specific gene expression programs. Given that oocytes are not mitotic after E13.5, and as we have previously demonstrated equivalent oocyte densities in Taf4b-deficient and wild-type ovaries at E18.5 [19], these data likely reflect alterations in gene expression and not reduced germ cell numbers. Accordingly, MVH-stained E13.5 ovaries display relatively equivalent numbers of germ cells across Taf4b genotypes (S5 Fig). Proper TAF4b regulation thus leads to the proper expression of downstream genes regulating multiple stages of meiosis I including onset, synapsis, recombination and arrest.


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 expression of meiosis genes in E13.5 Taf4b-deficient ovaries: Quantitative RT-PCR was used to compare differential gene expression between E13.5 wild-type and Taf4b-deficient ovary cDNA. RT-PCR was performed in technical triplicate and values were normalized to 18S rRNA with fold-change displayed after setting the wild-type value to 1.n = 4 wild-type animals and 3 Taf4b-deficient animals. Taf4b-deficient oocytes displayed about 25% of the Stra8, Sycp1, and Sycp2 mRNA expression of wild-type oocytes, while the somatic marker Wnt4 is not significantly changed between genotypes. Error bars represent SEM, and p-values were determined by Unpaired Student T-Test (* = p < 0.05; *** = p < 0.005).
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4920394&req=5

pgen.1006128.g007: Reduced expression of meiosis genes in E13.5 Taf4b-deficient ovaries: Quantitative RT-PCR was used to compare differential gene expression between E13.5 wild-type and Taf4b-deficient ovary cDNA. RT-PCR was performed in technical triplicate and values were normalized to 18S rRNA with fold-change displayed after setting the wild-type value to 1.n = 4 wild-type animals and 3 Taf4b-deficient animals. Taf4b-deficient oocytes displayed about 25% of the Stra8, Sycp1, and Sycp2 mRNA expression of wild-type oocytes, while the somatic marker Wnt4 is not significantly changed between genotypes. Error bars represent SEM, and p-values were determined by Unpaired Student T-Test (* = p < 0.05; *** = p < 0.005).
Mentions: To better understand if meiotic onset may also be affected in Taf4b-deficient oocytes, mRNA expression of Stra8 was tested at E13.5, the developmental time at which it is first activated by RA [3]. Notably, Stra8 expression in Taf4b-deficient ovaries is approximately 25% of that expressed in wild-type ovaries at the same time (Fig 7). Genes downstream of Stra8, including Sycp1 and Sycp2, exhibit similar reduced expression, suggesting that TAF4b may be important for meiotic onset as well as progression through direct transcriptional modulation of Stra8. In contrast to these oocyte-specific genes, Wnt4 expression [36] is not significantly changed in Taf4b-deficient ovaries at this time, suggesting that TAF4b is specifically promoting oocyte-specific gene expression programs. Given that oocytes are not mitotic after E13.5, and as we have previously demonstrated equivalent oocyte densities in Taf4b-deficient and wild-type ovaries at E18.5 [19], these data likely reflect alterations in gene expression and not reduced germ cell numbers. Accordingly, MVH-stained E13.5 ovaries display relatively equivalent numbers of germ cells across Taf4b genotypes (S5 Fig). Proper TAF4b regulation thus leads to the proper expression of downstream genes regulating multiple stages of meiosis I including onset, synapsis, recombination and arrest.

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