| First Author | Kasper LH | Year | 2010 |
| Journal | EMBO J | Volume | 29 |
| Issue | 21 | Pages | 3660-72 |
| PubMed ID | 20859256 | Mgi Jnum | J:309470 |
| Mgi Id | MGI:6758315 | Doi | 10.1038/emboj.2010.235 |
| Citation | Kasper LH, et al. (2010) CBP/p300 double null cells reveal effect of coactivator level and diversity on CREB transactivation. EMBO J 29(21):3660-72 |
| abstractText | It remains uncertain how the DNA sequence of mammalian genes influences the transcriptional response to extracellular signals. Here, we show that the number of CREB-binding sites (CREs) affects whether the related histone acetyltransferases (HATs) CREB-binding protein (CBP) and p300 are required for endogenous gene transcription. Fibroblasts with both CBP and p300 knocked-out had strongly attenuated histone H4 acetylation at CREB-target genes in response to cyclic-AMP, yet transcription was not uniformly inhibited. Interestingly, dependence on CBP/p300 was often different between reporter plasmids and endogenous genes. Transcription in the absence of CBP/p300 correlated with endogenous genes having more CREs, more bound CREB, and more CRTC2 (a non-HAT coactivator of CREB). Indeed, CRTC2 rescued cAMP-inducible expression for certain genes in CBP/p300 null cells and contributed to the CBP/p300-independent expression of other targets. Thus, endogenous genes with a greater local concentration and diversity of coactivators tend to have more resilient-inducible expression. This model suggests how gene expression patterns could be tuned by altering coactivator availability rather than by changing signal input or transcription factor levels. |
