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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

Taf4b-deficient oocytes experience defective meiotic progression and chromosome asynapsis.Pachytene spreads were prepared using the drying-down technique (50) on cell suspensions from E16.5 wild-type (A-D; I-L) and Taf4b-deficient (E-H; M-P) ovaries. Slides were stained for SYCP1 and SYCP3 (A-H), or SYCP3 and CENP-A (I-P). White arrowheads in (H) indicate regions of asynapsis in which SYCP3 is localized but SYCP1 is not; while white arrowheads in (P) indicate regions of asynapsis, many of which can be visualized by non-overlapping CENP-A centromeric foci. Slides were also stained for γH2AX and SYCP3 (Q, R) to visualize double-strand breaks. A high incidence of asynapsis (S), as scored by >20 CENP-A foci, as well as defects in meiotic progression (T), as scored by SYCP3 configuration (S1 Fig), were apparent in Taf4b-deficient oocytes. *: n = 4 animals each, one-tailed t-test, p<0.05
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pgen.1006128.g002: Taf4b-deficient oocytes experience defective meiotic progression and chromosome asynapsis.Pachytene spreads were prepared using the drying-down technique (50) on cell suspensions from E16.5 wild-type (A-D; I-L) and Taf4b-deficient (E-H; M-P) ovaries. Slides were stained for SYCP1 and SYCP3 (A-H), or SYCP3 and CENP-A (I-P). White arrowheads in (H) indicate regions of asynapsis in which SYCP3 is localized but SYCP1 is not; while white arrowheads in (P) indicate regions of asynapsis, many of which can be visualized by non-overlapping CENP-A centromeric foci. Slides were also stained for γH2AX and SYCP3 (Q, R) to visualize double-strand breaks. A high incidence of asynapsis (S), as scored by >20 CENP-A foci, as well as defects in meiotic progression (T), as scored by SYCP3 configuration (S1 Fig), were apparent in Taf4b-deficient oocytes. *: n = 4 animals each, one-tailed t-test, p<0.05

Mentions: As many genes coordinately expressed with human TAF4B in the human fetal ovary are critical for the fidelity of meiosis I, we analyzed prophase I progression in Taf4b-deficient mouse oocytes. Strikingly, when visualized by two different immunofluorescence methods, E16.5 Taf4b-deficient oocytes exhibit high degrees of asynapsis and aberrant meiosis. One means to test synapsis is by visualizing chromosomal co-localization of Synaptonemal Complex Proteins 1 and 3, which coat the central and lateral elements, respectively [33]. Complete co-localization indicates faithful synapsis, as seen in wild-type oocytes (Fig 2A–2D), while regions of asynapsis only stain positively for SYCP3 and lack SYCP1, as observed in most Taf4b-deficient oocytes (Fig 2E–2H). Another means of testing synapsis is by counting chromosomal centromeric foci marked by Centromere Protein A (CENP-A) staining [34]. Complete synapsis of XX pachytene chromosomes will result in the appearance of 20 centromeric foci, as seen in wild-type oocytes (Fig 2I–2L), while regions of asynapsis will result in non-overlapped centromeres and the appearance of greater than 20 CENP-A foci as seen in most Taf4b-deficient oocytes (Fig 2M–2P). Persistent double strand breaks are also evident in Taf4b-deficient oocytes as visualized by the presence of the histone variant γH2AX on pachytene chromosomes (Fig 2Q and 2R). Notably, nearly 75% of Taf4b-deficient oocytes exhibit some degree of asynapsis during pachytene, a percentage significantly greater than that ever observed in wild-type oocytes (Fig 2S, p < 0.05).


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)

Taf4b-deficient oocytes experience defective meiotic progression and chromosome asynapsis.Pachytene spreads were prepared using the drying-down technique (50) on cell suspensions from E16.5 wild-type (A-D; I-L) and Taf4b-deficient (E-H; M-P) ovaries. Slides were stained for SYCP1 and SYCP3 (A-H), or SYCP3 and CENP-A (I-P). White arrowheads in (H) indicate regions of asynapsis in which SYCP3 is localized but SYCP1 is not; while white arrowheads in (P) indicate regions of asynapsis, many of which can be visualized by non-overlapping CENP-A centromeric foci. Slides were also stained for γH2AX and SYCP3 (Q, R) to visualize double-strand breaks. A high incidence of asynapsis (S), as scored by >20 CENP-A foci, as well as defects in meiotic progression (T), as scored by SYCP3 configuration (S1 Fig), were apparent in Taf4b-deficient oocytes. *: n = 4 animals each, one-tailed t-test, p<0.05
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4920394&req=5

pgen.1006128.g002: Taf4b-deficient oocytes experience defective meiotic progression and chromosome asynapsis.Pachytene spreads were prepared using the drying-down technique (50) on cell suspensions from E16.5 wild-type (A-D; I-L) and Taf4b-deficient (E-H; M-P) ovaries. Slides were stained for SYCP1 and SYCP3 (A-H), or SYCP3 and CENP-A (I-P). White arrowheads in (H) indicate regions of asynapsis in which SYCP3 is localized but SYCP1 is not; while white arrowheads in (P) indicate regions of asynapsis, many of which can be visualized by non-overlapping CENP-A centromeric foci. Slides were also stained for γH2AX and SYCP3 (Q, R) to visualize double-strand breaks. A high incidence of asynapsis (S), as scored by >20 CENP-A foci, as well as defects in meiotic progression (T), as scored by SYCP3 configuration (S1 Fig), were apparent in Taf4b-deficient oocytes. *: n = 4 animals each, one-tailed t-test, p<0.05
Mentions: As many genes coordinately expressed with human TAF4B in the human fetal ovary are critical for the fidelity of meiosis I, we analyzed prophase I progression in Taf4b-deficient mouse oocytes. Strikingly, when visualized by two different immunofluorescence methods, E16.5 Taf4b-deficient oocytes exhibit high degrees of asynapsis and aberrant meiosis. One means to test synapsis is by visualizing chromosomal co-localization of Synaptonemal Complex Proteins 1 and 3, which coat the central and lateral elements, respectively [33]. Complete co-localization indicates faithful synapsis, as seen in wild-type oocytes (Fig 2A–2D), while regions of asynapsis only stain positively for SYCP3 and lack SYCP1, as observed in most Taf4b-deficient oocytes (Fig 2E–2H). Another means of testing synapsis is by counting chromosomal centromeric foci marked by Centromere Protein A (CENP-A) staining [34]. Complete synapsis of XX pachytene chromosomes will result in the appearance of 20 centromeric foci, as seen in wild-type oocytes (Fig 2I–2L), while regions of asynapsis will result in non-overlapped centromeres and the appearance of greater than 20 CENP-A foci as seen in most Taf4b-deficient oocytes (Fig 2M–2P). Persistent double strand breaks are also evident in Taf4b-deficient oocytes as visualized by the presence of the histone variant γH2AX on pachytene chromosomes (Fig 2Q and 2R). Notably, nearly 75% of Taf4b-deficient oocytes exhibit some degree of asynapsis during pachytene, a percentage significantly greater than that ever observed in wild-type oocytes (Fig 2S, p < 0.05).

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