Conserved Structure and Evolution of DPF Domain of PHF10—The Specific Subunit of PBAF Chromatin Remodeling Complex

Abstract

Transcription activation factors and multisubunit coactivator complexes get recruited at specific chromatin sites via protein domains that recognize histone modifications. Single PHDs (plant homeodomains) interact with differentially modified H3 histone tails. Double PHD finger (DPF) domains possess a unique structure different from PHD and are found in six proteins: histone acetyltransferases MOZ and MORF; chromatin remodeling complex BAF (DPF1–3); and chromatin remodeling complex PBAF (PHF10). Among them, PHF10 stands out due to the DPF sequence, structure, and functions. PHF10 is ubiquitously expressed in developing and adult organisms as four isoforms differing in structure (the presence or absence of DPF) and transcription regulation functions. Despite the importance of the DPF domain of PHF10 for transcription activation, its structure remains undetermined. We performed homology modeling of the human PHF10 DPF domain and determined common and distinct features in structure and histone modifications recognition capabilities, which can affect PBAF complex chromatin recruitment. We also traced the evolution of DPF1–3 and PHF10 genes from unicellular to vertebrate organisms. The data reviewed suggest that the DPF domain of PHF10 plays an important role in SWI/SNF-dependent chromatin remodeling during transcription activation.

The TRIPLE PHD FINGERS proteins are required for SWI/SNF complex-mediated +1 nucleosome positioning and 5’ transcript length determination in Arabidopsis

“…Among them, we found two paralogs of an evolutionarilyconserved signature subunit -SMARCG-that we named TRIPLE PHD FINGERS (TPF1 and TFP2) and that have not been characterized in plants. These proteins are distant orthologs of the metazoan DOBLE PHD FINGERS(DPF)/PHD FINGER PROTEIN 10 (PHF10) family and the fungal SWP82/Rsc7 proteins (46)(47)(48). Functional characterization of the DPF/PHF10 proteins in mammals has demonstrated their important function in the complex through dynamic incorporation upon different cellular contexts and its role in the recruitment of the complex to the chromatin mediated by their tandem PHD histone reader domains (46,49,50).…”

PHD finger protein 10 promotes cell proliferation by regulating CD44 transcription in gastric cancer

“…The human PHF10 protein (also known as BAF45A) is a homolog of the Drosophila transcription co-activator SAYP with a SAY domain at N-terminal and two zinc finger domains at C-terminal [ 10 , 11 ]. The two zinc finger domains are also called PHD domains.…”

A novel chromatin-remodeling complex variant, dcPBAF, is involved in maintaining transcription in differentiated neurons

“…BRD7 and PBRM1 contain bromodomains (BDs) which bind acetylated lysine residues on histones, whereas PHF10 contains the C-terminal double PHD finger (DPF) domain. The PHD domains of DPF are tandemly organized in a face‐to‐back manner in a single structure that interacts with histone N‐termini differently from a single PHD ( Local et al, 2018 ; Soshnikova et al, 2020 ; Chugunov et al, 2021 ).…”