{Reference Type}: Journal Article
{Title}: Trim66's paternal deficiency causes intrauterine overgrowth.
{Author}: Mielnicka M;Tabaro F;Sureka R;Acurzio B;Paoletti R;Scavizzi F;Raspa M;Crevenna AH;Lapouge K;Remans K;Boulard M;
{Journal}: Life Sci Alliance
{Volume}: 7
{Issue}: 7
{Year}: 2024 Jul
{Factor}: 5.781
{DOI}: 10.26508/lsa.202302512
{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 the TRIM66 PHD-Bromodomain binds to H3 N-terminus only when lysine 4 is unmethylated. We addressed TRIM66's role in reproduction by loss-of-function genetics in the mouse. Males homozygous for Trim66-null mutations produced functional spermatozoa. Round spermatids lacking TRIM66 up-regulated a network of genes involved in histone acetylation and H3K4 methylation. Profiling of H3K4me3 patterns in the sperm produced by the 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.