Identification of proteome-wide and functional analysis of lysine crotonylation in multiple organs of the human fetus.

Lysine crotonylation (Kcr) is a novel post-translational modification that is important in functional studies. However, our understanding of Kcr in the developing human fetus brain, heart, kidney, liver, and lung remains restricted. In this study, we used high-resolution LC-MS/MS and high-sensitivity immunoaffinity purification to analyze Kcr in the brain, heart, kidney, liver, and lung of 17-week fetus. A total of 24,947 Kcr modification sites were identified in 5,102 proteins, resulting in the most diverse Kcr proteome of fetus organs ever reported. We investigated the universality and specificity of Kcr during the development of several organs in 17-week fetus using bioinformatics analysis. Kcr proteins were found to be closely associated with the synthesis, transcription and translation of genetic material, energy production and metabolic processes. Importantly, the expression of Kcr proteins in each organ was closely related to the organs' developmental functions. Furthermore, several highly modified Kcr proteins may be important targets during fetus organ development. This discovery advances our understanding of fetus organ development and establishes the groundwork for future research into the regulatory mechanisms of crotonylation in fetus organ development.