Regulating histone acetyltransferases and deacetylases

Abstract

Histone acetyltransferases and histone deacetylases regulate the acetylation of histones and transcription factors, and in doing so have major roles in the control of cell fate. Many recent results have indicated that their function is strictly regulated in cells through the modulation of their levels, activity and availability for interaction with specific transcription factors. In this review, we present the various molecular mechanisms that bring about this tight regulation and discuss how these regulatory events influence cellular responses to environmental changes.

Figure 1

Model of local action of histone acetyltransferases and histone deacetylases. Histone acetyltransferases (HATs) and histone deacetylases (HDACs) are recruited to their target promoters through a physical interaction with a sequence-specific transcription factor (TF). They usually function within a multimolecular complex ('enzymatic complex'), in which the other subunits are necessary for them to modify nucleosomes around the binding site. These enzymes can also modify factors other than histones (protein X) to regulate transcription. Note that the position of the modified nucleosome that is shown has been chosen at random for this figure.

Figure 2

Functional 'code' of CREB-binding protein/p300 post-translational modifications. Representation of the CREB-binding protein (CBP) and p300 histone acetyl transferases including their functional domains (cysteine/histidine-rich domains (CH1 and CH3); CREB-binding domain (KIX); bromodomain (Br); and acetyl transferase domain (AT)) and some of their post-translational modifications (phosphorylation (P); methylation (Met); and sumoylation (Sumo)). The post-translational modifications activating (in green) or inhibiting (in red) CBP or p300 enzymatic activity (filled circles) or transcriptional activity (empty circles) are shown. The transcription factors for which binding to CBP or p300 is affected by CBP/p300 modifications are also shown. Note that some modifications have only been documented for CBP or for p300. The lines below some modifications indicate the region in which the modification occurs for sites that have not been fully characterized. NR, nuclear receptor superfamily.

D.T. is the recipient of an EMBO Young Investigator Award