Novel NuA4 subunits reveal a crucial role of dynamic expression of the negative arm of the circadian clock

ABSTRACT: Post-translational modifications (PTMs) on histones have been found to play diverse functions in regulating chromatin events and gene expression. The operation of circadian clocks heavily relies on finely tuned and timely expression of the proteins comprising core oscillators. However, most studies of PTMs' effects on circadian clocks have been conducted using static systems in which circadian clocks are rendered arrhythmic due to the essential role of PTMs on gene expression. In the Neurospora circadian system, the White Collar Complex (WCC), a heterodimeric transcription factor formed from White Collar-1 (WC-1) and White Collar-2 (WC-2), serves the function of the BMAL1/CLOCK heterodimer in mammals, driving expression of circadian negative arm component(s), a principal one in Neurospora encoded by the gene frequency (frq). FRQ interacts with FRH (FRQ-interacting helicase) and CK-1 forming a stable complex that represses its own expression by inhibiting WCC. In this study, a genetic screen identified a gene, designated as eaf-8, that encodes a novel conserved subunit of the NuA4 histone acetylation complex. Loss of eaf-8 reduces H4 acetylation and RNA polymerase (Pol) II occupancy at frq and other known circadian genes, and leads to a long circadian period, delayed phase, and defective overt circadian output at some temperatures. In addition to strongly associating with the NuA4 histone acetyltransferase complex, EAF-8 is also found complexed with the transcription elongation regulator BYE-1. Expression of eaf-8, bye-1, histone hH2Az, and several NuA4 subunits is controlled by the circadian clock, indicating that the molecular clock both regulates the basic chromatin status and is regulated by changes in chromatin. Taken together, our data identify a new type of the NuA4 complex including EAF-8 and BYE-1 which, along with conventional NuA4 subunits, is required for timely and dynamic frq expression and thereby a normal and persistent circadian rhythm.

INSTRUMENT(S): LTQ Orbitrap, Orbitrap Fusion

ORGANISM(S): Neurospora Crassa (ncbitaxon:5141)

SUBMITTER: Arminja Kettenbach  

PROVIDER: MSV000089415 | MassIVE | Wed May 04 04:50:00 BST 2022

SECONDARY ACCESSION(S): PXD033576

REPOSITORIES: MassIVE