Expansion of the ISWI chromatin remodeler family with new active complexes

Abstract

ISWI chromatin remodelers mobilize nucleosomes to control DNA accessibility. Complexes isolated to date pair one of six regulatory subunits with one of two highly similar ATPases. However, we find that each endogenously expressed ATPase co-purifies with every regulatory subunit, substantially increasing the diversity of ISWI complexes, and we additionally identify BAZ2B as a novel, seventh regulatory subunit. Through reconstitution of catalytically active human ISWI complexes, we demonstrate that the new interactions described here are stable and direct. Finally, we profile the nucleosome remodeling functions of the now expanded family of ISWI chromatin remodelers. By revealing the combinatorial nature of ISWI complexes, we provide a basis for better understanding ISWI function in normal settings and disease.

Hepatitis Delta Virus histone mimicry drives the recruitment of chromatin remodelers for viral RNA replication

“…S-HDAg acetylation by the histone acetyl transferase p300 in the nucleus is mediated by the transcription factor YY1 and the interaction with a multiprotein complex of high molecular weight 22 . Here we show that the S-HDAg acetylation motif K72acXXR mimics the histone KacXXR SLiM and is read by the BRD of the BAZ2B protein, the regulatory subunit of the BRF chromatin remodeling complexes 18 . BAZ2B was identified by MS as one of the top 30 proteins that co-precipitate with the SNF2L and/or SNF2H ATPases 18 .…”

“…Here we show that the S-HDAg acetylation motif K72acXXR mimics the histone KacXXR SLiM and is read by the BRD of the BAZ2B protein, the regulatory subunit of the BRF chromatin remodeling complexes 18 . BAZ2B was identified by MS as one of the top 30 proteins that co-precipitate with the SNF2L and/or SNF2H ATPases 18 . Although both ATPases confer nucleosome-sliding activity to the BRF-1 and the BRF-5 complexes, respectively, an alternative splicing can generate a catalytically inactive SNF2L (ex13) variant in humans 19 .…”

“…BAZ2B has been recently described as a novel ISWI regulatory subunit of the chromatin remodeler BRF due to its association with the human ATPases SNF2L/SMARCA1 (BRF-1 complex) and SNF2H/SMARCA5 (BRF-5 complex) (Supplementary Fig. 3) 18 . MS analysis also detected 6 and 11 unique tryptic peptides spanning the full-length SNF2L (P28370) and SNF2H (O60264) proteins, respectively.…”

High-resolution glycosylation site-engineering method identifies MICA epitope critical for shedding inhibition activity of anti-MICA antibodies

“…After C18 clean up, dried and reconstituted samples were chromatographically separated and analyzed on a hybrid Elite Orbitrap mass spectrometer (Thermo Fisher Scientific) using conditions described previously. 43 Resultant spectra were interrogated against in silico digestions. Oxidation of Cysteine, Tryptophan, Tyrosine, Methionine, Phenylalanine, Histidine, Arginine, Leucine and Isoleucine were quantified by measuring areas under the curve of the matching modified ions versus total occurrence of a given peptide.…”

Chromatin remodeling: a complex affair

“…The human ISWI subfamily of remodelers has been defined as a group of more than six different enzyme complexes where one of two related ATP ase subunits (Snf2L/ SMARCA 1 and Snf2H/ SMARCA 5) is paired with one of six different accessory subunits. In this issue of EMBO Reports , Oppikofer et al find that the human ISWI subfamily is even more polymorphic in nature—every known accessory subunit can interact and function with both ATP ase isoforms. This raises the complexity of the human ISWI subfamily to > 12 distinct enzymes, with the possibility for much higher levels of combinatorial assemblies, and has the potential to create enzymes with novel biochemical activities, as well as novel regulatory wiring through differential interactions with locus‐specific factors or histone modifications.…”