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 | |
| State | Published - Aug 22 2008 |
| Externally published | Yes |
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Cite this
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 journal › Article
}
TY - JOUR
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.
UR - http://www.scopus.com/inward/record.url?scp=50149094330&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=50149094330&partnerID=8YFLogxK
U2 - 10.1126/science.1155544
DO - 10.1126/science.1155544
M3 - Article
C2 - 18719283
AN - SCOPUS:50149094330
VL - 321
SP - 1084
EP - 1085
JO - Science
JF - Science
SN - 0036-8075
IS - 5892
ER -