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

Taranjit Singh Rai, Aastha Puri, Tony McBryan, Jason Hoffman, Yong Tang, Nikolay A. Pchelintsev, John van Tuyn, Ronen Marmorstein, David C. Schultz, Peter D. Adams

Research output: Contribution to journalArticle

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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.

LanguageEnglish
Pages4107-4118
Number of pages12
JournalMolecular and Cellular Biology
Volume31
Issue number19
DOIs
Publication statusPublished - 1 Oct 2011

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Histone Chaperones
Histones
Yeasts
Chromatin
Overlapping Genes
Human Genome
Regulator Genes
DNA Replication
Recombinant Proteins
Transcriptional Activation
Saccharomyces cerevisiae
Genes
Proteins

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Rai, T. S., Puri, A., McBryan, T., Hoffman, J., Tang, Y., Pchelintsev, N. A., ... 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), 4107-4118. https://doi.org/10.1128/MCB.05546-11
Rai, Taranjit Singh ; Puri, Aastha ; McBryan, Tony ; Hoffman, Jason ; Tang, Yong ; Pchelintsev, Nikolay A. ; van Tuyn, John ; Marmorstein, Ronen ; Schultz, David C. ; Adams, Peter D. / Human CABIN1 is a functional member of the human HIRA/UBN1/ASF1a Histone H3.3 chaperone complex. In: Molecular and Cellular Biology. 2011 ; Vol. 31, No. 19. pp. 4107-4118.
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Rai, TS, Puri, A, McBryan, T, Hoffman, J, Tang, Y, Pchelintsev, NA, van Tuyn, J, Marmorstein, R, Schultz, DC & Adams, PD 2011, 'Human CABIN1 is a functional member of the human HIRA/UBN1/ASF1a Histone H3.3 chaperone complex', Molecular and Cellular Biology, vol. 31, no. 19, pp. 4107-4118. https://doi.org/10.1128/MCB.05546-11

Human CABIN1 is a functional member of the human HIRA/UBN1/ASF1a Histone H3.3 chaperone complex. / Rai, Taranjit Singh; Puri, Aastha; McBryan, Tony; Hoffman, Jason; Tang, Yong; Pchelintsev, Nikolay A.; van Tuyn, John; Marmorstein, Ronen; Schultz, David C.; Adams, Peter D.

In: Molecular and Cellular Biology, Vol. 31, No. 19, 01.10.2011, p. 4107-4118.

Research output: Contribution to journalArticle

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T1 - Human CABIN1 is a functional member of the human HIRA/UBN1/ASF1a Histone H3.3 chaperone complex

AU - Rai, Taranjit Singh

AU - Puri, Aastha

AU - McBryan, Tony

AU - Hoffman, Jason

AU - Tang, Yong

AU - Pchelintsev, Nikolay A.

AU - van Tuyn, John

AU - Marmorstein, Ronen

AU - Schultz, David C.

AU - Adams, Peter D.

PY - 2011/10/1

Y1 - 2011/10/1

N2 - 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.

AB - 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.

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