TCFL5 deficiency impairs the pachytene to diplotene transition during spermatogenesis in the mouse

Galán-Martínez, Javier; Berenguer, Inés; Maza, Ma Del Carmen; Stamatakis, Konstantinos; Gironès, Núria; Fresno, Manuel

doi:10.1038/s41598-022-15167-w

Cited by 10 publications

(5 citation statements)

References 62 publications

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“…Consistent with the testis-specific expression of human Tcfl5 (Maruyama et al, 1998), two recent studies revealed TCFL5 is first expressed in mouse primary spermatocytes (Galán-Martínez et al, 2022;Xu et al, 2022). We used staged mouse testes (Nebel et al, 1961) to measure the abundance of Tcfl5 mRNA and protein across spermatogenesis.…”

Section: A-myb Is Expressed Before Tcfl5 During Male Meiosis Imentioning

confidence: 74%

A-MYB/TCFL5 regulatory architecture ensures the production of pachytene piRNAs in placental mammals

Biasini

Cecchini

et al. 2022

RNA

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In male mice, the transcription factor A MYB initiates the transcription of pachytene piRNA genes during meiosis. Here, we report that A MYB activates the transcription factor Tcfl5 produced in pachytene spermatocytes. Subsequently, A MYB and TCFL5 reciprocally reinforce their own transcription to establish a positive feedback circuit that triggers pachytene piRNA production. TCFL5 regulates the expression of genes required for piRNA maturation and promotes transcription of evolutionarily young pachytene piRNA genes, whereas A-MYB activates the transcription of older pachytene piRNA genes. Intriguingly, pachytene piRNAs from TCFL5-dependent young loci initiates the production of piRNAs from A-MYB-dependent older loci ensuring the self-propagation of pachytene piRNAs. A MYB and TCFL5 act via a set of incoherent feedforward loops that drive regulation of gene expression by pachytene piRNAs during spermatogenesis. This regulatory architecture is conserved in rhesus macaque, suggesting that it was present in the last common ancestor of placental mammals.

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Section: A-myb Is Expressed Before Tcfl5 During Male Meiosis Imentioning

confidence: 74%

A-MYB/TCFL5 regulatory architecture ensures the production of pachytene piRNAs in placental mammals

Biasini

Cecchini

et al. 2022

RNA

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“…Of these sixteen TF candidates with PGC-enriched transcript expression, only seven (Gata2, Mga, Nr6a1, Tbx4, Tcfl5, Tfap2c, and Zfx) showed enriched expression in germ cells when compared to the somatic compartment of the gonad, and thus met our requirements for further in silico investigation (Supplementary Figure 9a). These candidate TFs have reported roles in cell fate determination, growth and fertility regulation, and meiotic progression 79,80 , all of which are in line with the cellular events that occur as PGCs commit to the female pathway. Nonetheless, the chromatin binding and gene expression of GATA2, MGA, TBX4, TCFL5, and TFAP2c showed the clearest patterns of sexual dimorphism in E13.5 PGCs and represented the most compelling TF candidates (Fig.…”

Section: A Computational Approach To Identify Candidate Tfs Regulatin...mentioning

confidence: 74%

“…Of these TFs, TCFL5 and TFAP2C showed the strongest enriched expression in XX PGCs. TCFL5 binds to the promoters of meiotic genes such as Sycp1 (synapsis) and Stag3 (cohesion) during spermatogenesis in the mouse 79 . Tcfl5 is indispensable for the completion of meiosis and spermatid maturation 79 , and meiosis of female germ cells 81 .…”

Section: Discussionmentioning

confidence: 99%

“…TCFL5 binds to the promoters of meiotic genes such as Sycp1 (synapsis) and Stag3 (cohesion) during spermatogenesis in the mouse 79 . Tcfl5 is indispensable for the completion of meiosis and spermatid maturation 79 , and meiosis of female germ cells 81 . Our multiomics data also demonstrate strong Tfap2c expression and motif enrichment in XX PGCs beginning at E12.5 and continuing through E13.5.…”

Section: Molecular Signatures Of Differentiating Pgcs Revealed Diseas...mentioning

confidence: 99%

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Single-nucleus multiomics reveals the gene-regulatory networks underlying sex determination of murine primordial germ cells

Alexander,

Rodriguez,

Chen

et al. 2024

Preprint

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Accurate specification of female and male germ cells during embryonic development is critical for sexual reproduction. Primordial germ cells (PGCs) are the bipotential precursors of mature gametes that commit to an oogenic or spermatogenic fate in response to sex-determining cues from the fetal gonad. The critical processes required for PGCs to integrate and respond to signals from the somatic environment in gonads are not understood. In this study, we developed the first single-nucleus multiomics map of chromatin accessibility and gene expression during murine PGC development in both XX and XY embryos. Profiling of cell-type specific transcriptomes and regions of open chromatin from the same cell captured the molecular signatures and gene networks underlying PGC sex determination. Joint RNA and ATAC data for single PGCs resolved previously unreported PGC subpopulations and cataloged a multimodal reference atlas of differentiating PGC clusters. We discovered that regulatory element accessibility precedes gene expression during PGC development, suggesting that changes in chromatin accessibility may prime PGC lineage commitment prior to differentiation. Similarly, we found that sexual dimorphism in chromatin accessibility and gene expression increased temporally in PGCs. Combining single-nucleus sequencing data, we computationally mapped the cohort of transcription factors that regulate the expression of sexually dimorphic genes in PGCs. For example, the gene regulatory networks of XX PGCs are enriched for the transcription factors, TFAP2c, TCFL5, GATA2, MGA, NR6A1, TBX4, and ZFX. Sex-specific enrichment of the forkhead-box and POU6 families of transcription factors was also observed in XY PGCs. Finally, we determined the temporal expression patterns of WNT, BMP, and RA signaling during PGC sex determination, and our discovery analyses identified potentially new cell communication pathways between supporting cells and PGCs. Our results illustrate the diversity of factors involved in programming PGCs towards a sex-specific fate.

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“…In the male meiotic prophase, developmental progression beyond the pachytene stage is a critical event in which multiple gene regulatory programs inactivate gene expression on sex chromosomes, suppress transposable elements, and progress toward the post-meiotic stage (Li et al 2013) (Sin et al 2015) (da Cruz et al 2016) (Ernst et al 2019). Accordingly, a subset of male germ cell-specific transcription factors is required for progression beyond the pachytene stage (Bolcun-Filas et al 2011) (Li et al 2013) (Oji et al 2020) (Horisawa-Takada et al 2021) (Oura et al 2021) (Xu et al 2022) (Galan-Martinez et al 2022) (Cecchini et al 2023). However, it remains unclear how pachytene progression is ensured in the male meiotic prophase and which transcription factors are responsible for this process.…”

Section: Introductionmentioning

confidence: 99%

Atypical heat shock transcription factor HSF5 is critical for male meiotic prophase under non-stress conditions

Yoshimura,

Shimada,

Kikuchi

et al. 2023

Preprint

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Meiotic prophase progression is differently regulated in males and females. In males, pachytene transition during meiotic prophase is accompanied by robust alteration in gene expression. However, how gene expression is regulated differently to ensure meiotic prophase completion in males remains elusive. Herein, we identified HSF5 as a male germ cell-specific heat shock transcription factor (HSF) for meiotic prophase progression. Genetic analyses and single-cell RNA-sequencing demonstrated that HSF5 is essential for progression beyond the pachytene stage under non-stress conditions rather than heat stress. Chromatin binding analysis in vivo and DNA-binding assays in vitro suggested that HSF5 binds to promoters in a subset of genes associated with chromatin organization. HSF5 recognizes a DNA motif different from typical heat shock elements recognized by other canonical HSFs. This study suggests that HSF5 is an atypical HSF that enforces the gene expression program for pachytene transition during meiotic prophase in males.

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TCFL5 deficiency impairs the pachytene to diplotene transition during spermatogenesis in the mouse

Cited by 10 publications

References 62 publications

A-MYB/TCFL5 regulatory architecture ensures the production of pachytene piRNAs in placental mammals

A-MYB/TCFL5 regulatory architecture ensures the production of pachytene piRNAs in placental mammals

Single-nucleus multiomics reveals the gene-regulatory networks underlying sex determination of murine primordial germ cells

Atypical heat shock transcription factor HSF5 is critical for male meiotic prophase under non-stress conditions

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