The citrullinating enzyme PADI4 governs progenitor cell proliferation and translation in developing hair follicles

ABSTRACT: Posttranslational protein modifications have emerged as a mechanism regulating progenitor cell state transitions during tissue formation. Herein, we exploit the stereotyped hair follicle development to delineate the function of PADI4; an enzyme converting peptidylarginine to citrulline. Single cell-sequencing places Padi4 in both progenitor and differentiated hair lineage cells and indicate that PADI4 acts to repress transcription during hair follicle development. We establish PADI4 as a negative regulator of proliferation, acting on LEF1-positive hair shaft committed progenitor cells. Mechanistically, PADI4 citrullinates proteins associated with mRNA-processing and ribosomal biogenesis, and lack of PADI4 promotes protein synthesis and rRNA transcription in vivo. Characterizing key translational effectors, we demonstrate that PADI4 citrullinates the translational repressor 4E-BP1 and reveal a crosstalk between PADI4 activity and 4E-BP1 phosphorylation. This work sheds new light on how posttranslational modifications impact progenitor cell states and tissue formation.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Keratinocyte, Skin

DISEASE(S): Disease Free

SUBMITTER: Maria Genander  

LAB HEAD: Maria Genander

PROVIDER: PXD064137 | Pride | 2025-07-28

REPOSITORIES: Pride