Abo1, a conserved bromodomain AAA ‐ ATP ase, maintains global nucleosome occupancy and organisation

Abstract

Maintenance of the correct level and organisation of nucleosomes is crucial for genome function. Here, we uncover a role for a conserved bromodomain AAA‐ATPase, Abo1, in the maintenance of nucleosome architecture in fission yeast. Cells lacking abo1 + experience both a reduction and mis‐positioning of nucleosomes at transcribed sequences in addition to increased intragenic transcription, phenotypes that are hallmarks of defective chromatin re‐establishment behind RNA polymerase II. Abo1 is recruited to gene sequences and associates with histone H3 and the histone chaperone FACT. Furthermore, the distribution of Abo1 on chromatin is disturbed by impaired FACT function. The role of Abo1 extends to some promoters and also to silent heterochromatin. Abo1 is recruited to pericentromeric heterochromatin independently of the HP1 ortholog, Swi6, where it enforces proper nucleosome occupancy. Consequently, loss of Abo1 alleviates silencing and causes elevated chromosome mis‐segregation. We suggest that Abo1 provides a histone chaperone function that maintains nucleosome architecture genome‐wide.

Regulation of nucleosome positioning by a CHD Type III chromatin remodeler and its relationship to developmental gene expression inDictyostelium

“…For nucleosome mapping, read-pairs were selected at a SAM format ISIZE of 150 bp (±30 bp) and filtered using a simple heuristic peak marker that reports the bins corresponding to nucleosome read midpoint frequency maxima above a noise threshold (Gal et al 2015). Frequency distributions of these read midpoints (representing the putative nucleosome dyad positions) were plotted relative to the Dictyostelium genome in 1-bp bins using read midpoint frequency distributions normalized to the average frequency value within the sequence window and rendered with the Integrated Genome Browser (IGB) (Nicol et al 2009).…”

“…Heatmaps were rendered in Java TreeView (Saldanha 2004). For determining differences in nucleosome positions, nucleosome dyad frequency data were smoothed to minimize noise using an Epanechnikov kernel density estimate (Kernel Estimation-0.05 with bandwidth = 30) (Gal et al 2015). Nonmatching peak-summits, defined as variances of greater than twofold in peak frequency or >10-bp mismatch in peak summit position, were determined in comparison of two data sets (e.g., growth/development, WT/chdC nulls).…”

Bromodomain AAA+ ATPases get into shape

“…ATAD2 is proposed to function as transcriptional co-factor of several oncogenic transcription factors, including Myc, estrogen and androgen receptors [2]. Abo1/ ATAD2 is also a putative histone chaperone [3,4], it is linked to DNA replication [5], heterochromatin boundary maintenance [6,7] and transcription programs in ES cells [8]. Abo1 and ATAD2 can thus be added to a range of chromatin-interacting proteins of relevance in cancer biology, yet little is known about their function in mechanistic terms.…”

“…generate some histone-DNA intermediates that require other factors to complete the assembly task. Interestingly, Abo1 was shown to be synthetic lethal with a mutant of the conserved and essential histone chaperone FACT [3]. This suggests potential cooperation between the two factors.…”

“…In this regard, mass spectrometry of endogenous histones bound to Abo1/ATAD2 might reveal the specific histone modification(s) recognized by this protein. Moreover, since Abo1/ATAD2 co-purifies with several chromatin complexes [3,8], it is possible that similarly to Rvb AAA+ ATPases, Abo1 and its homologs participate in the assembly and/or remodeling activities of other chromatin bound complexes [10].…”