Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P10412 (H1.4)
 75 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Global changes in the phosphorylation state of human H1 isoforms isolated from UL3 cells have been investigated using mass spectrometry. Relative changes in H1 phosphorylation between untreated cells and cells treated with dexamethasone or various CDK inhibitors were determined. The specific cyclin-dependent kinase consensus sites of phosphorylation on the histone H1 isoforms that show changes in phosphorylation were also investigated. Three sites of phosphorylation on histone H1.4 isoforms have been identified.
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PMID:Global changes in and characterization of specific sites of phosphorylation in mouse and human histone H1 Isoforms upon CDK inhibitor treatment using mass spectrometry. 1841 67

Splicing factor 3B1 (SF3B1) is a core splicing protein that stabilizes the interaction between the U2 snRNA and the branch point in the mRNA target during splicing. SF3B1 is heavily phosphorylated at its N terminus and a substrate of cyclin-dependent kinases (CDKs). Although SF3B1 phosphorylation coincides with splicing catalysis, the functional significance of SF3B1 phosphorylation is largely undefined. Here, we show that SF3B1 phosphorylation follows a dynamic pattern during cell cycle progression that depends on CDK activity. SF3B1 is known to interact with chromatin, and we found that SF3B1 maximally interacts with nucleosomes during G1/S and that this interaction requires CDK2 activity. In contrast, SF3B1 disassociates from nucleosomes at G2/M, coinciding with a peak in CDK1-mediated SF3B1 phosphorylation. Thus, CDK1 and CDK2 appear to have opposing roles in regulating SF3B1-nucleosome interactions. Importantly, these interactions were modified by the presence and phosphorylation status of linker histone H1, particularly the H1.4 isoform. Performing genome-wide analysis of SF3B1-chromatin binding in synchronized cells, we observed that SF3B1 preferentially bound exons. Differences in SF3B1 chromatin binding to specific sites, however, did not correlate with changes in RNA splicing, suggesting that the SF3B1-nucleosome interaction does not determine cell cycle-dependent changes to mRNA splicing. Our results define a cell cycle stage-specific interaction between SF3B1 and nucleosomes that is mediated by histone H1 and depends on SF3B1 phosphorylation. Importantly, this interaction does not seem to be related to SF3B1's splicing function and, rather, points toward its potential role as a chromatin modifier.
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PMID:Cyclin-dependent kinase 1 (CDK1) and CDK2 have opposing roles in regulating interactions of splicing factor 3B1 with chromatin. 2976 37