Human CABIN1 Is a functional member of the human HIRA/UBN1/ASF1a histone H3.3 chaperone complex

Rai, T., Puri, A., McBryan, T., Hoffman, J., Tang, Y., Pchelintsev, N.A., van Tuyn, J., Marmorstein, R., Schultz, D.C. and Adams, P.D. (2011) Human CABIN1 Is a functional member of the human HIRA/UBN1/ASF1a histone H3.3 chaperone complex. Molecular and Cellular Biology, 31(19), pp. 4107-4118. (doi: 10.1128/MCB.05546-11)

Full text not currently available from Enlighten.

Abstract

The mammalian HIRA/UBN1/ASF1a complex is a histone chaperone complex that is conserved from yeast (Saccharomyces cerevisiae) to humans. This complex preferentially deposits the histone variant H3.3 into chromatin in a DNA replication-independent manner and is implicated in diverse chromatin regulatory events from gene activation to heterochromatinization. In yeast, the orthologous complex consists of three Hir proteins (Hir1p, Hir2p, and Hir3p), Hpc2p, and Asf1p. Yeast Hir3p has weak homology to CABIN1, a fourth member of the human complex, suggesting that Hir3p and CABIN1 may be orthologs. Here we show that HIRA and CABIN1 interact at ectopic and endogenous levels of expression in cells, and we isolate the quaternary HIRA/UBN1/CABIN1/ASF1a (HUCA) complex, assembled from recombinant proteins. Mutational analyses support the view that HIRA acts as a scaffold to bring together UBN1, ASF1a, and CABIN1 into a quaternary complex. We show that, like HIRA, UBN1, and ASF1a, CABIN1 is involved in heterochromatinization of the genome of senescent human cells. Moreover, in proliferating cells, HIRA and CABIN1 regulate overlapping sets of genes, and these genes are enriched in the histone variant H3.3. In sum, these data demonstrate that CABIN1 is a functional member of the human HUCA complex and so is the likely ortholog of yeast Hir3p.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Rai, Dr Taranjit and Adams, Professor Peter and McBryan, Dr Anthony
Authors: Rai, T., Puri, A., McBryan, T., Hoffman, J., Tang, Y., Pchelintsev, N.A., van Tuyn, J., Marmorstein, R., Schultz, D.C., and Adams, P.D.
College/School:College of Science and Engineering > School of Chemistry
Journal Name:Molecular and Cellular Biology
ISSN:0270-7306

University Staff: Request a correction | Enlighten Editors: Update this record