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bioRxiv · 10.1101/2024.02.12.579976

Trim66 paternal deficiency causes intrauterine overgrowth

Mielnicka, M.·Tabaro, F.·Sureka, R.·Acurzio, B.·Paoletti, R.·Scavizzi, F.·Raspa, M.·Crevenna, A. H.·Lapouge, K.·Remans, K.·Boulard, M.
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Abstract

The tripartite motif-containing protein 66 (TRIM66, also known as TIF1-delta) is a PHD-Bromo containing protein primarily expressed in post-meiotic male germ cells known as spermatids. Biophysical assays showed that TRIM66 PHD-Bromo domain binds to H3 N-terminus only when lysine 4 is unmethylated. We addressed TRIM66s role in reproduction by loss-of-function genetics in the mouse. Males homozygous for Trim66-null mutations produced functional spermatozoa. Round spermatids lacking TRIM66 upregulated a network of genes involved in histone acetylation and H3K4 methylation. Profiling of H3K4me3 patterns in the sperm produced by Trim66-null mutant showed minor alterations below statistical significance. Unexpectedly, Trim66-null males, but not females, sired pups overweight at birth, hence revealing that Trim66 mutations cause a paternal effect phenotype.

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Mielnicka, M., Tabaro, F., Sureka, R., Acurzio, B., Paoletti, R., Scavizzi, F., Raspa, M., Crevenna, A. H., Lapouge, K., Remans, K., Boulard, M.. 2024-02-14. Trim66 paternal deficiency causes intrauterine overgrowth. https://doi.org/10.1101/2024.02.12.579976

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