%0 Journal Article
%T Trim66's paternal deficiency causes intrauterine overgrowth.
%A Mielnicka M
%A Tabaro F
%A Sureka R
%A Acurzio B
%A Paoletti R
%A Scavizzi F
%A Raspa M
%A Crevenna AH
%A Lapouge K
%A Remans K
%A Boulard M
%J Life Sci Alliance
%V 7
%N 7
%D 2024 Jul
%M 38719749
%F 5.781
%R 10.26508/lsa.202302512
%X 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.