The sequential phosphorylation of PHF10 subunit of the PBAF chromatin remodeling complex determines different properties of the PHF10 isoforms

Abstract

The mammalian PBAF subfamily of SWI/SNF chromatin remodeling complexes plays a wide role in the regulation of gene expression. PHF10 is a subunit of the signature module of PBAF, responsible for its interaction with chromatin. PHF10 is represented by four different isoforms, which are alternatively incorporated in the complex. Two of PHF10 isoforms lacking C-terminal PHD domains contain a cluster of phosphorylated serine residues, designated as X-cluster. In the present study, we explore the phosphorylation of the X-cluster in detail. We identified additional phosphorylated serine residues and designated them as either frequently or rarely phosphorylated. The X-cluster consists of two independently phosphorylated subclusters. Phosphorylation of the second subcluster depends on phosphorylation of a primary serine 327. These two subclusters surround a sequence, which is predicted to be a nuclear localization sequence (NLS3). The NLS3 does not affect localization of PHF10 isoforms. However, it is essential for X-cluster phosphorylation and increased stability of isoforms that lack PHD. Conversely, the presence of NLS3 signal in isoforms that contain C-terminal PHD domains reduces their stability. Thus, phosphorylation of PHF10 isoforms regulates their cell level, determining the rate of incorporation in PBAF. This may alter the pattern of PBAF regulated genes.

CRISPR-RfxCas13d screening uncovers Bckdk as a post-translational regulator of the maternal-to-zygotic transition in teleosts

“…Although pBAF is rather a reader of H3K27ac than a complex involved in the deposit of this epigenetic mark, its alteration can lead to a reduced transcription and a lower histone acetylation [78][79][80] . Interestingly, Phf10 phosphorylation has been reported to affect its stability in mammalian cells 81,82 . However, we did not detect Phf10 in our proteome likely due to the differential level of resolution of proteomic and phospho-proteomic approaches.…”

Optical chemosensors for the detection of proximally phosphorylated peptides and proteins

“…5,6 It has been widely observed that differing phosphorylation patterns can lead to different protein interactions with distinct biological outcomes. 7 Proximal phosphorylation has been shown to affect many cellular functions including protein localization, 8 degradation, 9 signaling cascades, 10,11 gene expression, [12][13][14] and the cell cycle (Fig. 1B).…”