# Cooperative and Opposing Functions of ANP32E and VPS72 Govern Gene Promoter Chromatin Status

## TL;DR

This study explores how two proteins, VPS72 and ANP32E, work together and in opposition to control gene activity by influencing chromatin structure.

## Contribution

The study reveals a new paradigm where opposing functions of VPS72 and ANP32E regulate gene promoter chromatin status.

## Key findings

- VPS72 promotes H2A.Z incorporation and transcription, while ANP32E stabilizes nucleosomes and limits these effects.
- Loss of ANP32E increases chromatin accessibility and transcription, which is reversed by co-depleting VPS72.
- ANP32E promotes nucleosome assembly and prevents DNA unwrapping, supporting its in vivo role.

## Abstract

The histone variant H2A.Z resides within active gene promoters, but how it influences chromatin state and nucleosome stability remains poorly understood. Here, we probe two H2A.Z binding proteins with seemingly opposing function: VPS72, an SRCAP subunit that aids in H2A.Z deposition, and ANP32E, a histone chaperone which is thought to remove H2A.Z. Using functional genomics and biochemical assays, we show that VPS72 and ANP32E co-occupy active promoters yet function antagonistically. VPS72 promotes H2A.Z incorporation, acetylation, BRG1 recruitment, and transcription, whereas ANP32E constrains these features by stabilizing nucleosomes. Loss of ANP32E increases VPS72 binding, chromatin accessibility, and transcription, while co-depletion of VPS72 reverses these effects. Reconstitution assays show that ANP32E promotes nucleosome assembly and prevents DNA unwrapping, providing a mechanistic basis for in vivo function. Our results support a model where promoter accessibility arises from antagonistic and cooperative actions, revealing a general paradigm in which counterbalancing factors govern gene regulatory potential.