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

• Published in: Biology open Vol. 9; no. 1; p. 439431
• Main Authors: Sheynov, Andrey A, Tatarskiy, Jr, Victor V, Tatarskiy, Eugene V, Nabirochkina, Elena N, Georgieva, Sofia G, Soshnikova, Nataliya V
• Format: Journal Article
• Language: English
• Published: England The Company of Biologists Ltd 01-01-2020; The Company of Biologists
• Subjects: Chromatin remodeling; cluster phosphorylation; Clusters; Domains; Gene expression; Isoforms; Kinases; Localization; multiple phosphorylation; pbaf chromatin remodeling complex; phf10 isoforms; Phosphorylation; Residues; Serine; Stability; Multiple phosphorylation; PBAF chromatin remodeling complex; PHF10 isoforms; Cluster phosphorylation
• ISSN: 2046-6390; 2046-6390
• DOI: 10.1242/bio.043943

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.