Epigenetics in Cardiac Disease by Johannes Backs & Timothy A. McKinsey

Author:Johannes Backs & Timothy A. McKinsey
Language: eng
Format: epub
Publisher: Springer International Publishing, Cham

A very large number of transcription factors, as well as components of the basal transcriptional machinery, interact physically and functionally with the KAT3s (Kasper and Brindle 2006; Abraham et al. 1993). More than 300 different transcription factor partners have been identified for CBP and p300, and dozens of these are direct substrates (Goodman and Smolik 2000). Extensive redundancy between p300 and CBP exists for these interactions and probably between the KAT3 proteins and other coactivators, including the KAT2 family (GCN5/PCAF) (Phan et al. 2005).

The transcription programs for which the KAT3 proteins are indispensable are specialized and cell type-specific, such as inflammation, long-term memory formation (Alarcon et al. 2004), and hepatic gluconeogenesis (Zhou et al. 2004). KAT3s are also required for the transcriptional activation of immediate-early genes, through their rapid, dynamic acetylation of trimethylated lysine 4 on histone 3 (H3K4me3). This chromatin mark is associated with RNA polymerase II recruitment and transcriptional activation (Crump et al. 2011). Thus, rather than acting as general transcriptional integrators, the KAT3 proteins enable differentiated cell and organ functions and link extracellular signals to a rapid, complex transcriptional response (Lee et al. 2009).

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