Title: Human UBN1 Is an Ortholog of Yeast Hpc2p and Has an Essential Role in the HIRA/ASF1a Chromatin-Remodeling Pathway in Senescent Cells
Authors: Banumathy, Gowrishankar ×
Somaiah, Neeta
Zhang, Rugang
Tang, Yong
Hoffmann, Jason
Andrake, Mark
Ceulemans, Hugo
Schultz, David
Marmorstein, Ronen
Adams, Peter D #
Issue Date: Feb-2009
Publisher: Amer soc microbiology
Series Title: Molecular and cellular biology vol:29 issue:3 pages:758-770
Abstract: Cellular senescence is an irreversible proliferation arrest, tumor suppression process and likely contributor to tissue aging. Senescence is often characterized by domains of facultative heterochromatin, called senescence-associated heterochromatin foci (SAHF), which repress expression of proliferation-promoting genes. Given its likely contribution to tumor suppression and tissue aging, it is essential to identify all components of the SAHF assembly pathway. Formation of SAHF in human cells is driven by a complex of histone chaperones, namely, HIRA and ASF1a. In yeast, the complex orthologous to HIRA/ASF1a contains two additional proteins, Hpc2p and Hir3p. Using a sophisticated approach to search for remote orthologs conserved in multiple species through evolution, we identified the HIRA-associated proteins, UBN1 and UBN2, as candidate human orthologs of Hpc2p. We show that the Hpc2-related domain of UBN1, UBN2, and Hpc2p is an evolutionarily conserved HIRA/Hir-binding domain, which directly interacts with the N-terminal WD repeats of HIRA/Hir. UBN1 binds to proliferation-promoting genes that are repressed by SAHF and associates with histone methyltransferase activity that methylates lysine 9 of histone H3, a site that is methylated in SAHF. UBN1 is indispensable for formation of SAHF. We conclude that UBN1 is an ortholog of yeast Hpc2p and a novel regulator of senescence.
ISSN: 0270-7306
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Biosignaling & Therapeutics
Faculty of Medicine - miscellaneous
× corresponding author
# (joint) last author

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