Abstract
The N-terminal region of adenovirus E1A interacts with histone acetyl transferases (HATs) such as p300, P/CAF, and GCN5. The C-terminal region interacts with the transcriptional corepressors CtBP1 and CtBP2. The functional significance of co-recruitment of HATs and CtBPs by E1A is not well understood. In this study, we have shown that E1A enhanced acetylation of CtBP2 by recruitment of p300 to the CtBP2 complex. Additionally, E1A also displaced the histone methyltransferase G9a and the E-box repressor ZEB from the CtBP2 complex through the C-terminal CtBP-binding domain. A transcriptional activation function encoded by the E1A N-terminal region was efficiently inhibited by CtBP2 but not by a mutant with an N-terminal deletion or by a mutant deficient in interaction with E1A. Two isoforms of CtBP1 (CtBP1-L and CtBP1-S) poorly inhibited transcriptional activity of the E1A N-terminal region. Thus, the N-terminal domain of CtBP2 may contribute a unique transcriptional regulatory activity of CtBP2. Our results provide new insights by which CtBP might modulate the biochemical activities of E1A.
Highlights
The transforming activities of E1A are critically dependent on the N-terminal 80-amino acid region encompassing CR1 and the region between amino acids 120 and 140 (CR2) [5]
The N-terminal 80-amino acid region interacts with the global transcriptional coactivators p300 and its paralog CBP, which function as histone acetyl transferases (HATs) (6 – 8)
A chromatin immunoprecipitation (ChIP) study has suggested that E1A-mediated targeting of HATs to promoters of cell cycle regulatory genes results in removal of the histone mark associated with transcriptional repression and addition of the mark characteristic of transcriptional activation during G0 3 G1 cell cycle progression [19]
Summary
The transforming activities of E1A are critically dependent on the N-terminal 80-amino acid region encompassing CR1 and the region between amino acids 120 and 140 (CR2) [5]. Enhancement by GST-E1A are specific events that can be HeLa cells stably expressing FLAG-HA-tagged CtBP2 were observed under a low acetyl-CoA concentration (radiolabeled) transfected with GFP-E1A or mutants with N-terminal (⌬N, as well as under a high acetyl-CoA concentration (non-radiola- E1A aa 2–74) or C-terminal (⌬C E1A aa 178 –238) deletions beled, Fig. 3D).
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