Chromatin accessibility profiling in Neurospora crassa reveals molecular features associated with accessible and inaccessible chromatin

Abstract

Background Regulation of chromatin accessibility and transcription are tightly coordinated processes. Studies in yeast and higher eukaryotes have described accessible chromatin regions, but little work has been done in filamentous fungi. Results Here we present a genome-scale characterization of accessible chromatin regions in Neurospora crassa, which revealed characteristic molecular features of accessible and inaccessible chromatin. We present experimental evidence of inaccessibility within heterochromatin regions in Neurospora, and we examine features of both accessible and inaccessible chromatin, including the presence of histone modifications, types of transcription, transcription factor binding, and relative nucleosome turnover rates. Chromatin accessibility is not strictly correlated with expression level. Accessible chromatin regions in the model filamentous fungus Neurospora are characterized the presence of H3K27 acetylation and commonly associated with pervasive non-coding transcription. Conversely, methylation of H3 lysine-36 catalyzed by ASH1 is correlated with inaccessible chromatin within promoter regions. Conclusions: In N. crassa, H3K27 acetylation is the most predictive histone modification for open chromatin. Conversely, our data show that H3K36 methylation is a key marker of inaccessible chromatin in gene-rich regions of the genome. Our data are consistent with an expanded role for H3K36 methylation in intergenic regions of filamentous fungi compared to the model yeasts, S. cerevisiae and S. pombe, which lack homologs of the ASH1 methyltransferase.

New insights into genome annotation in Podospora anserina through re-exploiting multiple RNA-seq data

“…Although a fairly large number of complete annotated fungal genome sequences is available [17], no such gene model has been built to date for filamentous fungi. Still, a recent assay for Transposase-Accessible Chromatin sequencing (ATAC-seq) performed in Neurospora crassa highlights the diversity of promoter structures and evidenced that histone acetylation and small RNA production are correlated with accessible chromatin, whereas some histone methylations are correlated with inaccessible chromatin [18].…”

Polycomb Repressive Complex 2 in Eukaryotes—An Evolutionary Perspective

“…H3K27me3 in telomeres resides in gene-containing regions, and it is neighbored by non-overlapping H3K9me3 marking gene depleted, DNA-methylated regions [ 111 , 235 ]. Interestingly, H3K27me3-marked loci represent only a small subset of inaccessible regions of chromatin as determined by ATAC-seq, and H3K36me, rather than H3K27me3, is a predictive mark of chromatin inaccessibility in gene-rich regions in N. crassa [ 239 ].…”

Epigenetic Activation of Silent Biosynthetic Gene Clusters in Endophytic Fungi Using Small Molecular Modifiers

“…Consequently, genetic deletion of,HDACs in various fungal species such as Aspergillus fumigatus, Aspergillus oryzae, Fusarium fujikuroi, Penicillium oryzae, Fusarium asiaticum, P. chrysogenum, and A. nidulans have resulted in increased expression of known gene clusters and expression of novel clusters that are repressed in the control strain (Albright et al, 2015;Collemare and Seidl, 2019). Generally, acetylation of histones (e.g., H3K27ac in Neurospora crassa) is associated with transcriptional activation of SM gene clusters (Ferraro et al, 2021;Zhang et al, 2021). Although the exact mechanism of this activation is not known, there are various proposed mechanisms suggested by observations of histone marks in different genetic analysis studies (Gacek-Matthews et al, 2016;Ferraro et al, 2021).…”

“…Generally, acetylation of histones (e.g., H3K27ac in Neurospora crassa ) is associated with transcriptional activation of SM gene clusters ( Ferraro et al, 2021 ; Zhang et al, 2021 ). Although the exact mechanism of this activation is not known, there are various proposed mechanisms suggested by observations of histone marks in different genetic analysis studies ( Gacek-Matthews et al, 2016 ; Ferraro et al, 2021 ).…”

“…Generally, acetylation of histones (e.g., H3K27ac in Neurospora crassa ) is associated with transcriptional activation of SM gene clusters ( Ferraro et al, 2021 ; Zhang et al, 2021 ). Although the exact mechanism of this activation is not known, there are various proposed mechanisms suggested by observations of histone marks in different genetic analysis studies ( Gacek-Matthews et al, 2016 ; Ferraro et al, 2021 ). The earlier proposed mechanism is that histone marks such as acetylation of histones neutralizes the positive charge of the ε-amino group of lysine in the nucleosome, thus weakening the interaction between the core histones with negatively charged DNA and subsequent chromatic accessibility ( Gacek-Matthews et al, 2016 ).…”