Global Analysis of Lysine 2‑Hydroxyisobutyrylome upon SAHA Treatment and Its Relationship with Acetylation and Crotonylation

Lysine 2-hydroxyisobutyrylation is
a newly discovered protein acylation
and was reported to share acyltransferases and deacylases with the
widely studied lysine acetylation. The well-known acetyltransferase
Tip60 and histone deacetylases HDAC 2 and HDAC 3 were discovered to
be “writer” and “eraser” of this new PTM
on histones. However, the acyltransferases and deacylases for nonhistone
proteins are still unclear. In this work, lysine 2-hydroxyisobutyrylome
on both histones and nonhistone proteins upon SAHA treatment were
intensively studied and 8765 lysine 2-hydroxyisobutyrylation sites
on 2484 proteins were identified in A549 cells. This is the largest
data set of lysine 2-hydroxyisobutyrylome in mammalian cells to date.
It was found that lysine 2-hydroxyisobutyrylation participates in
varieties of biological functions and processes including ribosome,
glycolysis/gluconeogenesis, and transcription. More importantly, it
was found that most quantified sites on core histones were up-regulated
upon SAHA treatment for all 2-hydroxyisobutyrylation, crotonylation,
and acetylation and the fold changes upon SAHA of 2-hydroxyisobutyrylation
and crotonylation on nonhistone proteins were highly correlated, while
their fold changes have little correlations with acetylation on nonhistone
proteins.