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TEX15 safeguards neuronal diversity in the mouse olfactory system

ABSTRACT: Animals detect diverse chemicals using hundreds of chemoreceptor proteins. In many organisms, sensory chemoreceptors obey a one-receptor-type-per-cell rule, which organizes information gathered by sensory neurons1. A key question remains how receptor expression gets diversified so that hundreds of chemoreceptors get expressed across the population of sensory neurons2–4. Here we show that diverse odorant receptor (OR) expression in mice depends on testis expressed gene 15 (Tex15). We find that Tex15 regulates OR expression in neuronal precursor cells. In Tex15 deficient (Tex15-/-) mice, OR transcript levels are increased in precursors, a handful of early-transcribed OR genes get expressed at abnormally high levels, and these ORs come to dominate the olfactory sensory neuron population. This results in a profound reduction in the diversity of OR gene choice as well as disrupted spatial patterning of the olfactory epithelium, without disrupting the one-receptor-type-per-cell rule. Tex15 encodes a transcriptional repressor5, and we show that Tex15-/- mice have reduced heterochromatin-associated H3K9me3 on OR genes. Thus, we propose that Tex15 directs a heterochromatin-based transcriptional repression mechanism that prevents uneven transcriptional onset from skewing OR choice. This mechanism safeguards the cellular diversity that is essential for broadly tuned chemosensation.

ORGANISM(S): Mus musculus

PROVIDER: GSE341836 | GEO | 2026/08/26

REPOSITORIES: GEO

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Tex15 is required for vomeronasal sensory neuron diversity and enables male pheromone detection

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2026-04-15 | GSE326692 | GEO

Expression profiling of Tex15 wt, Tex15 ht and Tex15 ko germ cells

Project description:We repport the effect of Tex15 inactivation on the transcriptome of male germ cells at embryonic day 16.5 (e16.5), 18.5 (e18.5), and postnatal day 2 (d2). We find upregulation of a large number of transposable elements in Tex15-/- germ cells.

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Expression profiling of Tex15 ht and Tex15 ko germ cells

Project description:We repport the effect of Tex15 inactivation on the transcriptome of male germ cells at embryonic day 16.5 (e16.5), 18.5 (e18.5), and postnatal day 2 (d2). We find a large number of differentially expressed genes between Tex15-deficient and Tex15 heterozygous germ cells at e18.5 and d2 but much fewer differentially expressed genes at e16.5.

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Whole genome bisulfite sequencing (WGBS) of Tex15 wt, Tex15 ht, and Tex15 ko male germ cells at postnatal day 2.5

Project description:DNA methylation is a major silencing mechanism of transposable elements (TEs). Here we report that TEX15, a testis-specific protein, is required for TE silencing. Through WGBS, we find that Tex15 mutant germ cells exhibit DNA hypomethylation in TEs. Our results identify TEX15 as a new essential epigenetic regulator that appears to function independently or downstream of the piRNA biogenesis machineries to silence TEs by DNA methylation in male germ cells.

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Expression profiling of Tex15 wt, Tex15 ht and Tex15 ko germ cells

Project description:Expression profiling of Tex15 wt, Tex15 ht and Tex15 ko germ cells

| PRJNA589898 | ENA

TEX15 silences transposable elements in male germ cells

Project description:This SuperSeries is composed of the SubSeries listed below. DNA methylation is a major silencing mechanism of transposable elements (TEs). Here we report that TEX15, a testis-specific protein, is required for TE silencing. TEX15 is both cytoplasmic and nuclear in embryonic germ cells and functions during genome-wide epigenetic reprogramming. Tex15 mutant exhibits DNA hypomethylation in TEs at a level similar to Mili but not Miwi2 mutant. As loss of Tex15 causes TE de-silencing without abolishing piRNA production, our results identify TEX15 as a new essential epigenetic regulator that appears to function independently or downstream of the piRNA biogenesis machineries to silence TEs by DNA methylation in male germ cells.

2020-05-18 | GSE140571 | GEO

TEX15 is an essential executor of MIWI2-directed transposon DNA methylation and silencing.

Project description:The PIWI protein MIWI2 and its associated PIWI-interacting RNAs (piRNAs) instruct DNA methylation of young active transposable elements (TEs) in the male germline. Here we show that MIWI2 associates with TEX15 in foetal gonocytes. TEX15 is predominantly a nuclear protein that is not required for piRNA biogenesis but is essential for piRNA-directed TE de novo methylation and silencing. In summary, TEX15 is an essential executor of mammalian piRNA-directed DNA methylation.

2020-06-17 | E-MTAB-9090 | biostudies-arrayexpress

HP1B and H3K9me3 Regulate Olfactory Receptor Choice and 2 Transcriptional Identity [ChIP-seq]

Project description:Diverse epigenetic regulatory mechanisms ensure and regulate cellular diversity. Among others, the histone 3 lysine 9 me3 (H3K9me3) post translational modification participates in silencing lineage-inappropriate genes. H3K9me3 restricts access of transcription factors and other regulatory proteins to genes that control cell fate. Mouse olfactory sensory neurons (OSN) select to express one olfactory receptor (OR) gene out of 2,600 possibilities. This monoallelic and stochastic OR choice happens as OSNs differentiate and undergo dramatic changes in nuclear architecture. OR genes from different chromosomes converge into specialized nuclear bodies and chromatin compartments, as H3K9me3 and chromatin binding proteins including heterochromatin protein 1 (HP1) are incorporated. In this work, we have uncovered an unexpected role for HP1b in OR choice and neuronal identity that cannot be rescued by HP1a in vivo. With the use of a conditional knock-in mouse model that replaces HP1b for HP1a, we observe changes in H3K9me3 levels and DNA accessibility over OR gene clusters. These changes alter the expression paTerns that partition the mouse olfactory epithelium into five OR expression zones, which results in a reduced OR repertoire leading to a loss of olfactory sensory neuron diversity. We propose that HP1b modulates the competition of OR-promoters for enhancers to promote receptor diversity, by establishing repression gradients in a zonal fashion.

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HP1B and H3K9me3 Regulate Olfactory Receptor Choice and 2 Transcriptional Identity [RNA-Seq]

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Epigenetic control of transposable elements in the mouse male germ line by Tex15

Project description:The piRNA biogenesis was evaluated in the mouse testes lacking TEX15. Total small RNAs, MILI-, and MIWI2-associated small RNAs from control (Tex15+/-) and Tex15(-/-) knock-out testes were sequenced. Data analysis revealed that the abundance of miRNAs and piRNAs was comparable between control and Tex15 knock-out testes, suggesting that loss of TEX15 function does not impair piRNA biogenesis. However, the relative abundance of MILI- and MIWI2-bound sense piRNAs derived from transposable elements was increased.

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