RT Journal Article
SR Electronic
T1 Single residue substitution in protamine 1 disrupts sperm genome packaging and embryonic development in mice
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.09.16.460631
DO 10.1101/2021.09.16.460631
A1 Lindsay Moritz
A1 Samantha B. Schon
A1 Mashiat Rabbani
A1 Yi Sheng
A1 Devon F. Pendlebury
A1 Ritvija Agrawal
A1 Caleb Sultan
A1 Kelsey Jorgensen
A1 Xianing Zheng
A1 Adam Diehl
A1 Kaushik Ragunathan
A1 Yueh-Chiang Hu
A1 Jayakrishnan Nandakumar
A1 Jun Z. Li
A1 Alan P. Boyle
A1 Kyle E. Orwig
A1 Sy Redding
A1 Saher Sue Hammoud
YR 2021
UL http://biorxiv.org/content/early/2021/09/16/2021.09.16.460631.abstract
AB Conventional dogma presumes that protamine-mediated DNA compaction in sperm is achieved by passive electrostatics between DNA and the arginine-rich core of protamines. However, phylogenetic analysis reveals several non-arginine residues that are conserved within, but not across, species. The functional significance of these residues or post-translational modifications are poorly understood. Here, we investigated the functional role of K49, a rodent-specific lysine residue in mouse protamine 1 (P1) that is acetylated early in spermiogenesis and retained in sperm. In vivo, an alanine substitution (P1 K49A) results in ectopic histone retention, decreased sperm motility, decreased male fertility, and in zygotes, premature P1 removal from paternal chromatin. In vitro, the P1 K49A substitution decreases protamine-DNA binding and alters DNA compaction/decompaction kinetics. Hence, a single amino acid substitution outside the P1 arginine core is sufficient to profoundly alter protein function and developmental outcomes, suggesting that protamine non-arginine residues are essential to ensure reproductive fitness.Competing Interest StatementThe authors have declared no competing interest.