CREBBPEP300

CREBBPEP300 is a term used to refer collectively to two closely related transcriptional coactivators in humans: CREBBP (CREB-binding protein) and EP300 (also known as p300). Both proteins are large, multi-domain transcriptional coactivators that function as epigenetic regulators by linking signal transduction pathways to chromatin remodeling and gene expression. They are encoded by separate genes, CREBBP and EP300, but share substantial sequence similarity and overlapping roles, and are frequently studied together as part of the CBP/p300 coactivator family.

Function and mechanism

CREBBP and EP300 act as transcriptional coactivators for a wide range of transcription factors, including CREB, p53, NF-κB, and elements of the developmental signaling networks. They possess intrinsic histone acetyltransferase (HAT) activity, which acetylates histones to promote an open chromatin configuration and facilitate transcription. In addition to histones, they acetylate non-histone proteins involved in DNA repair, cell cycle control, and metabolic regulation. Their activity is modulated by post-translational modifications and interactions with other chromatin remodelers, allowing integration of multiple cellular signals.

Structure

Both proteins feature conserved domain architectures that support their coactivator function: activating domains, a KIX domain that binds phosphorylated transcription factors, TAZ1 and TAZ2 domains, a bromodomain that recognizes acetyl-lysine marks, and a HAT catalytic domain. The modular structure enables recruitment to diverse enhancers and promoters.

Clinical significance

Mutations or haploinsufficiency of CREBBP or EP300 cause Rubinstein-Taybi syndrome, characterized by distinctive facial features, broad thumbs, and developmental delay. Somatic alterations in these genes are observed in various cancers, and pharmacological inhibition of CBP/p300 HAT activity is under investigation as a therapeutic strategy. In research, CREBBP and EP300 are often examined together due to their functional redundancy and cooperative roles in gene regulation.

See also

CBP/p300 coactivators; histone acetyltransferases; Rubinstein-Taybi syndrome.