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Series GSE166104 Query DataSets for GSE166104
Status Public on Jan 11, 2023
Title The Testis-Specific Transcription Factor TCFL5 Responds to A-MYB to Elaborate Male Meiotic Program in Mammals
Organisms Macaca mulatta; Mus musculus
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Non-coding RNA profiling by high throughput sequencing
Summary In the mammalian testis, the pool of spermatogonia is amplified by mitosis before these progenitor germ cells undergo meiosis to generate the haploid cells that give rise to sperm. Extensive changes in the transcriptome accompany the onset of the pachytene stage of meiosis, including the transcriptional activation of meiotic genes, the pachytene piRNA pathway, as well as mRNAs required later during spermiogenesis. How transcription is regulated to ensure the precise timing of this major reprogramming of gene expression remains largely uncharacterized. Here, we report that the testis-specific transcription factor TCFL5 is initially activated by the transcription factor A-MYB during meiosis. Subsequently, A-MYB and TCFL5 mutually reinforce their own transcription establishing a central regulatory circuit that regulates meiosis and spermiogenesis, as well as mediates pachytene piRNA production. TCFL5 drives the transcription of 476 genes required for meiosis including genes encoding pachytene piRNA biogenesis proteins, and 796 genes required for spermiogenesis. Tcfl5−/− mutant mice are sterile and spermatogenesis arrests at the mid- or late-pachytene stage of meiosis. Intriguingly, Tcfl5 haploinsufficiency leads to reduced male fertility suggesting germ cells are sensitive to Tcfl5 dosage to develop. Compromised TCFL5 expression underlies the reduced fertility phenotype directly or indirectly through regulating other transcription factors in Tcfl5+/− mutant mice. TCFL5 drives the transcription of evolutionarily younger pachytene piRNAs, while A-MYB regulates older pachytene piRNAs. Older and younger piRNAs mutually initiate their own processing providing evidence how these selfish genetic elements hijack meiotic transcriptional network to amplify themselves. We also demonstrate that TCFL5-mediated regulation of male meiosis and piRNA production is conserved in macaque. Our data establish a direct role of TCFL5 in ensuring the simultaneous activation of genes required for meiosis and spermiogenesis in mammals.
Overall design CUT&RUN, ChIPseq and RNAseq for adult male mouse germ cells or adult mouse testis
Contributor(s) Deniz OM, Tianxiong Y, Zhiping W, Zamore PD
Citation(s) 36241367, 36395073
Submission date Feb 03, 2021
Last update date Jan 12, 2023
Contact name Tianxiong Yu
Organization name Umass Med
Street address 364 Plantation St
City Worcester
State/province MA
ZIP/Postal code 01605
Country USA
Platforms (2)
GPL19057 Illumina NextSeq 500 (Mus musculus)
GPL21120 Illumina NextSeq 500 (Macaca mulatta)
Samples (57)
GSM5061804 CUTRUN-TCFL5-pachyteneCell-rep1
GSM5061805 CUTRUN-TCFL5-pachyteneCell-rep2
GSM5061806 CUTRUN-NEG-pachyteneCell-rep1
BioProject PRJNA699268
SRA SRP304560

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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE166104_RAW.tar 9.7 Gb (http)(custom) TAR (of BW)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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