A SIRT7-dependent acetylation switch regulates early B cell differentiation and lineage commitment through Pax5.

ABSTRACT: B lymphopoiesis is orchestrated by lineage-specific transcription factors. In B cell progenitors, lineage commitment is mediated by Pax5, which is commonly mutated in B cell acute lymphoblastic leukemia. Despite its essential role in immunity, the mechanisms regulating Pax5 function remain largely unknown. Here, we found that the NAD⁺-dependent enzyme SIRT7 coordinates B cell development through deacetylation of Pax5 at K198, which promotes Pax5 protein stability and transcriptional activity. Neither Pax5^K198 deacetylated nor acetylated mimics rescued B cell differentiation in Pax5^-/- pro-B cells, suggesting that B cell development requires Pax5 dynamic deacetylation. The Pax5^K198 deacetylation mimic restored lineage commitment in Pax5^-/-

SUBMITTER: Gamez-Garcia A 

PROVIDER: S-EPMC11588656 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature