Adenovirus small e1a alters global patterns of histone modification

Gregory A. Horwitz; Kangling Zhang; Matthew A. McBrian; Michael Grunstein; Siavash K. Kurdistani; Arnold J. Berk

doi:10.1126/science.1155544

Adenovirus small e1a alters global patterns of histone modification

Gregory A. Horwitz, Kangling Zhang, Matthew A. McBrian, Michael Grunstein, Siavash K. Kurdistani, Arnold J. Berk

Research output: Contribution to journal › Article › peer-review

179 Scopus citations

Abstract

Adenovirus small early region 1a (e1a) protein drives cells into S phase by binding RB family proteins and the closely related histone acetyl transferases p300 and CBP. The interaction with RB proteins displaces them from DNA-bound E2F transcription factors, reversing their repression of cell cycle genes. However, it has been unclear how the e1a interaction with p300 and CBP promotes passage through the cell cycle. We show that this interaction causes a threefold reduction in total cellular histone H3 lysine 18 acetylation (H3K18ac). CBP and p300 are required for acetylation at this site because their knockdown causes specific hypoacetylation at H3K18. SV40 T antigen also induces H3K18 hypoacetylation. Because global hypoacetylation at this site is observed in prostate carcinomas with poor prognosis, this suggests that processes resulting in global H3K18 hypoacetylation may be linked to oncogenic transformation.

Original language	English (US)
Pages (from-to)	1084-1085
Number of pages	2
Journal	Science
Volume	321
Issue number	5892
DOIs	https://doi.org/10.1126/science.1155544
State	Published - Aug 22 2008
Externally published	Yes

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title = "Adenovirus small e1a alters global patterns of histone modification",

abstract = "Adenovirus small early region 1a (e1a) protein drives cells into S phase by binding RB family proteins and the closely related histone acetyl transferases p300 and CBP. The interaction with RB proteins displaces them from DNA-bound E2F transcription factors, reversing their repression of cell cycle genes. However, it has been unclear how the e1a interaction with p300 and CBP promotes passage through the cell cycle. We show that this interaction causes a threefold reduction in total cellular histone H3 lysine 18 acetylation (H3K18ac). CBP and p300 are required for acetylation at this site because their knockdown causes specific hypoacetylation at H3K18. SV40 T antigen also induces H3K18 hypoacetylation. Because global hypoacetylation at this site is observed in prostate carcinomas with poor prognosis, this suggests that processes resulting in global H3K18 hypoacetylation may be linked to oncogenic transformation.",

author = "Horwitz, {Gregory A.} and Kangling Zhang and McBrian, {Matthew A.} and Michael Grunstein and Kurdistani, {Siavash K.} and Berk, {Arnold J.}",

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T1 - Adenovirus small e1a alters global patterns of histone modification

AU - Horwitz, Gregory A.

AU - Zhang, Kangling

AU - McBrian, Matthew A.

AU - Grunstein, Michael

AU - Kurdistani, Siavash K.

AU - Berk, Arnold J.

PY - 2008/8/22

Y1 - 2008/8/22

N2 - Adenovirus small early region 1a (e1a) protein drives cells into S phase by binding RB family proteins and the closely related histone acetyl transferases p300 and CBP. The interaction with RB proteins displaces them from DNA-bound E2F transcription factors, reversing their repression of cell cycle genes. However, it has been unclear how the e1a interaction with p300 and CBP promotes passage through the cell cycle. We show that this interaction causes a threefold reduction in total cellular histone H3 lysine 18 acetylation (H3K18ac). CBP and p300 are required for acetylation at this site because their knockdown causes specific hypoacetylation at H3K18. SV40 T antigen also induces H3K18 hypoacetylation. Because global hypoacetylation at this site is observed in prostate carcinomas with poor prognosis, this suggests that processes resulting in global H3K18 hypoacetylation may be linked to oncogenic transformation.

AB - Adenovirus small early region 1a (e1a) protein drives cells into S phase by binding RB family proteins and the closely related histone acetyl transferases p300 and CBP. The interaction with RB proteins displaces them from DNA-bound E2F transcription factors, reversing their repression of cell cycle genes. However, it has been unclear how the e1a interaction with p300 and CBP promotes passage through the cell cycle. We show that this interaction causes a threefold reduction in total cellular histone H3 lysine 18 acetylation (H3K18ac). CBP and p300 are required for acetylation at this site because their knockdown causes specific hypoacetylation at H3K18. SV40 T antigen also induces H3K18 hypoacetylation. Because global hypoacetylation at this site is observed in prostate carcinomas with poor prognosis, this suggests that processes resulting in global H3K18 hypoacetylation may be linked to oncogenic transformation.

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Adenovirus small e1a alters global patterns of histone modification

Abstract

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