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 journalArticle

139 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)1084-1085
Number of pages2
JournalScience
Volume321
Issue number5892
DOIs
StatePublished - Aug 22 2008
Externally publishedYes

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Histone Code
Adenoviridae
Acetylation
Histones
E2F Transcription Factors
Polyomavirus Transforming Antigens
cdc Genes
Proteins
Transferases
S Phase
Lysine
Prostate
Cell Cycle
Carcinoma
DNA

ASJC Scopus subject areas

  • General

Cite this

Horwitz, G. A., Zhang, K., McBrian, M. A., Grunstein, M., Kurdistani, S. K., & Berk, A. J. (2008). Adenovirus small e1a alters global patterns of histone modification. Science, 321(5892), 1084-1085. https://doi.org/10.1126/science.1155544

Adenovirus small e1a alters global patterns of histone modification. / Horwitz, Gregory A.; Zhang, Kangling; McBrian, Matthew A.; Grunstein, Michael; Kurdistani, Siavash K.; Berk, Arnold J.

In: Science, Vol. 321, No. 5892, 22.08.2008, p. 1084-1085.

Research output: Contribution to journalArticle

Horwitz, GA, Zhang, K, McBrian, MA, Grunstein, M, Kurdistani, SK & Berk, AJ 2008, 'Adenovirus small e1a alters global patterns of histone modification', Science, vol. 321, no. 5892, pp. 1084-1085. https://doi.org/10.1126/science.1155544
Horwitz GA, Zhang K, McBrian MA, Grunstein M, Kurdistani SK, Berk AJ. Adenovirus small e1a alters global patterns of histone modification. Science. 2008 Aug 22;321(5892):1084-1085. https://doi.org/10.1126/science.1155544
Horwitz, Gregory A. ; Zhang, Kangling ; McBrian, Matthew A. ; Grunstein, Michael ; Kurdistani, Siavash K. ; Berk, Arnold J. / Adenovirus small e1a alters global patterns of histone modification. In: Science. 2008 ; Vol. 321, No. 5892. pp. 1084-1085.
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