Epigenetic activation of CD274/PD-L1 by the MSL complex expands its role beyond dosage compensation.

ABSTRACT:

Introduction

The regulation of CD274 (PD-L1), a pivotal immune checkpoint in cancer immunotherapy, remain incompletely understood. The male-specific lethal (MSL) complex, initially identified in Drosophila dosage compensation, contains the core subunit KAT8 (MOF), which catalyzes histone H4 lysine 16 acetylation (H4K16ac). However, whether the MSL complex directly regulates CD274 transcription has not been established.

Methods

Using TIMER and GEPIA2, we charted pan-cancer expression of MSL subunits and their correlation with immune infiltration, integrating Kaplan-Meier survival and copy number variation (CNV) data to assess clinical relevance. CRISPR-Cas9 deletion of MSL1 or MSL3 in HEK293T cells, followed by RNA-seq, identified CD274 as a potential target. MSL1 knoc

SUBMITTER: Wen A 

PROVIDER: S-EPMC12705358 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature