Interplay among ATP-Dependent Chromatin Remodelers Determines Chromatin Organisation in Yeast

Abstract

Cellular DNA is packaged into chromatin, which is composed of regularly-spaced nucleosomes with occasional gaps corresponding to active regulatory elements, such as promoters and enhancers, called nucleosome-depleted regions (NDRs). This chromatin organisation is primarily determined by the activities of a set of ATP-dependent remodeling enzymes that are capable of moving nucleosomes along DNA, or of evicting nucleosomes altogether. In yeast, the nucleosome-spacing enzymes are ISW1 (Imitation SWitch protein 1), Chromodomain-Helicase-DNA-binding (CHD)1, ISW2 (Imitation SWitch protein 2) and INOsitol-requiring 80 (INO80); the nucleosome eviction enzymes are the SWItching/Sucrose Non-Fermenting (SWI/SNF) family, the Remodeling the Structure of Chromatin (RSC) complexes and INO80. We discuss the contributions of each set of enzymes to chromatin organisation. ISW1 and CHD1 are the major spacing enzymes; loss of both enzymes results in major chromatin disruption, partly due to the appearance of close-packed di-nucleosomes. ISW1 and CHD1 compete to set nucleosome spacing on most genes. ISW1 is dominant, setting wild type spacing, whereas CHD1 sets short spacing and may dominate on highly-transcribed genes. We propose that the competing remodelers regulate spacing, which in turn controls the binding of linker histone (H1) and therefore the degree of chromatin folding. Thus, genes with long spacing bind more H1, resulting in increased chromatin compaction. RSC, SWI/SNF and INO80 are involved in NDR formation, either directly by nucleosome eviction or repositioning, or indirectly by affecting the size of the complex that resides in the NDR. The nature of this complex is controversial: some suggest that it is a RSC-bound “fragile nucleosome”, whereas we propose that it is a non-histone transcription complex. In either case, this complex appears to serve as a barrier to nucleosome formation, resulting in the formation of phased nucleosomal arrays on both sides.

Essential histone chaperones collaborate to regulate transcription and chromatin integrity

“…Although we do not know the exact impact of this change on chromatin in our mutants, such a change might affect higher-order chromatin folding, chromatin compaction, and DNA accessibility (Correll et al, 2012; Li et al, 2016),possibly leading to some of the transcriptional defects observed in spt6-YW . Such an increase in inter-nucleosome distances has been observed in several other classes of mutants, including mutations that impair the chromatin remodelers Isw1, Isw2, Ino80, and Chd1 (Prajapati et al, 2020), as well as the Hir complex (Vasseur et al, 2016), a histone chaperone, and Yta7, a chromatin associated protein (Lombardi et al, 2011). Interestingly, we show that inactivation of one of these remodelers, Chd1, rescues spt6-YW and spn1-K192N mutant phenotypes (Table S2).…”

The yeast ISW1b ATP-dependent chromatin remodeler is critical for nucleosome spacing and dinucleosome resolution

“…Nucleosomes restrict access to DNA and are potent inhibitors of transcription and other DNA-dependent processes in vitro. Cells regulate access to their DNA in part by deploying ATP-dependent chromatin remodeling complexes that are capable of overcoming the nucleosome, either by removing it from the DNA or by sliding it along the DNA 3 – 6 .…”

RSC primes the quiescent genome for hypertranscription upon cell cycle re-entry

“…The best-described role for RSC in regulating chromatin architecture and transcriptions is its ability to generate NDRs, by sliding or evicting nucleosomes [22][23][24].…”

“…The best-described role for RSC in regulating chromatin architecture and transcriptions is its ability to generate NDRs, by sliding or evicting nucleosomes [22–24]. Moving the +1 nucleosome allows for TATA binding protein (TBP) promoter binding and transcription initiation [25].…”