Actin-related protein 6 facilitates proneural protein-induced gene activation for rapid neural differentiation

Yun Ling Hsiao, Hui Wen Chen, Kuan Han Chen, Bertrand Chin Ming Tan, Chia Hsiang Chen, Haiwei Pi*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

Abstract

Neurogenesis is initiated by basic helix-loop-helix proneural proteins. Here, we show that Actin-related protein 6 (Arp6), a core component of the H2A.Z exchange complex SWR1, interacts with proneural proteins and is crucial for efficient onset of proneural protein target gene expression. Arp6 mutants exhibit reduced transcription in sensory organ precursors (SOPs) downstream of the proneural protein patterning event. This leads to retarded differentiation and division of SOPs and smaller sensory organs. These phenotypes are also observed in proneural gene hypomorphic mutants. Proneural protein expression is not reduced in Arp6 mutants. Enhanced proneural gene expression fails to rescue retarded differentiation in Arp6 mutants, suggesting that Arp6 acts downstream of or in parallel with proneural proteins. H2A.Z mutants display Arp6-like retardation in SOPs. Transcriptomic analyses demonstrate that loss of Arp6 and H2A.Z preferentially decreases expression of proneural protein-activated genes. H2A.Z enrichment in nucleosomes around the transcription start site before neurogenesis correlates highly with greater activation of proneural protein target genes by H2A.Z. We propose that upon proneural protein binding to E-box sites, H2A.Z incorporation around the transcription start site allows rapid and efficient activation of target genes, promoting rapid neural differentiation.

Original languageEnglish
Article numberdev201034
JournalDevelopment (Cambridge)
Volume150
Issue number5
DOIs
StatePublished - 01 03 2023

Bibliographical note

© 2023. Published by The Company of Biologists Ltd.

Keywords

  • Actin-related protein
  • Drosophila
  • Histone variant H2A.Z
  • Neurogenesis
  • Proneural protein
  • Basic Helix-Loop-Helix Transcription Factors/metabolism
  • Actins/metabolism
  • Transcriptional Activation
  • Arabidopsis/genetics
  • Nucleosomes/metabolism
  • Histones/metabolism
  • Arabidopsis Proteins/metabolism

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