Dataset Information

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.

SUBMITTER: Horwitz GA

PROVIDER: S-EPMC2756290 | biostudies-literature | 2008 Aug

REPOSITORIES: biostudies-literature

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Adenovirus small e1a alters global patterns of histone modification.

Horwitz Gregory A GA Zhang Kangling K McBrian Matthew A MA Grunstein Michael M Kurdistani Siavash K SK Berk Arnold J AJ

Science (New York, N.Y.) 20080801 5892

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 hist ...[more]

PMID: 18719283

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Project description:Herpesvirus latency is generally thought to be governed by epigenetic modifications, but the dynamics of viral chromatin at early timepoints of latent infection are poorly understood. Here, we report a comprehensive spatial and temporal analysis of epigenetic modifications during latent infection with Kaposi's sarcoma associated herpesvirus (KSHV), the etiologic agent of Kaposi's sarcoma and primary effusion lymphoma (PEL). Using high resolution tiling microarrays in conjunction with immunprecipitation of methylated DNA (MeDIP) and modified histones (ChIP), we have determined global patterns of epigenetic modifications across the KSHV genome in several tumor-derived cell lines as well as de novo infected endothelial cells, revealing highly distinct landscapes of epigenetic modifications associated with latent KSHV infection. We find that KSHV genomes are subject to profound methylation at CpG dinucleotides, leading to the establishment of characteristic global DNA methylation patterns. However, such patterns evolved slowly and thus are unlikely to govern latency early during the infection process. In contrast, we observed that latent histone modification patterns were rapidly established upon a de novo infection. Our analysis furthermore demonstrates that such patterns are not characterized by the absence of activating histone modifications, since both H3K9/K14-ac and H3K4-me3 marks were prominently detected at several loci, including the promoter of the lytic cycle transactivator Rta. While these regions were furthermore largely devoid of the constitutive heterochromatin marker H3K9-me3, we observed rapid and widespread deposition of H3K27-me3 across latent KSHV genomes, a bivalent modification which is able to repress transcription despite of the simultaneous presence of activating marks. Our findings suggest that the epigenetic patterns identified here induce a poised state of repression during viral latency, which can be rapidly reversed once the lytic cycle is induced. This dataset contains our ChIP-on-chip data; the MeDIP data are deposited in a separate dataset.

Dataset Information

Adenovirus small e1a alters global patterns of histone modification.

Publications

Adenovirus small e1a alters global patterns of histone modification.

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