Writers and readers of H3K9me2 form distinct protein networks during the cell cycle that include candidates for H3K9 mimicry. Biosci Rep 2023 Oct 31;43(10)
Date
10/02/2023Pubmed ID
37782747Pubmed Central ID
PMC10611923DOI
10.1042/BSR20231093Scopus ID
2-s2.0-85175273435 (requires institutional sign-in at Scopus site) 1 CitationAbstract
Histone H3 lysine 9 methylation (H3K9me), which is written by the Euchromatic Histone Lysine Methyltransferases EHMT1 and EHMT2 and read by the heterochromatin protein 1 (HP1) chromobox (CBX) protein family, is dysregulated in many types of cancers. Approaches to inhibit regulators of this pathway are currently being evaluated for therapeutic purposes. Thus, knowledge of the complexes supporting the function of these writers and readers during the process of cell proliferation is critical for our understanding of their role in carcinogenesis. Here, we immunopurified each of these proteins and used mass spectrometry to define their associated non-histone proteins, individually and at two different phases of the cell cycle, namely G1/S and G2/M. Our findings identify novel binding proteins for these writers and readers, as well as corroborate known interactors, to show the formation of distinct protein complex networks in a cell cycle phase-specific manner. Furthermore, there is an organizational switch between cell cycle phases for interactions among specific writer-reader pairs. Through a multi-tiered bioinformatics-based approach, we reveal that many interacting proteins exhibit histone mimicry, based on an H3K9-like linear motif. Gene ontology analyses, pathway enrichment, and network reconstruction inferred that these comprehensive EHMT and CBX-associated interacting protein networks participate in various functions, including transcription, DNA repair, splicing, and membrane disassembly. Combined, our data reveals novel complexes that provide insight into key functions of cell cycle-associated epigenomic processes that are highly relevant for better understanding these chromatin-modifying proteins during cell cycle and carcinogenesis.
Author List
Pollin G, De Assuncao TM, Doria Jorge S, Chi YI, Charlesworth MC, Madden B, Iovanna J, Zimmermann MT, Urrutia R, Lomberk GAuthors
Young-In Chi PhD Assistant Professor in the Surgery department at Medical College of WisconsinGwen Lomberk PhD Professor in the Surgery department at Medical College of Wisconsin
Thiago Milech De Assuncao Research Scientist II in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin
Gareth Pollin PhD Postdoctoral Researcher 3 in the Surgery department at Medical College of Wisconsin
Raul A. Urrutia MD Center Director, Professor in the Surgery department at Medical College of Wisconsin
Michael T. Zimmermann PhD Director, Assistant Professor in the Data Science Institute department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
CarcinogenesisCell Cycle
Cell Division
Histocompatibility Antigens
Histone-Lysine N-Methyltransferase
Histones
Humans
Lysine