JMY forms a complex with EP300 (p300) (Shikama et al. 1999). TTC5 (Strap) interacts with both JMY and EP300 and facilitates the recruitment of JMY to EP300 (Demonacos et al. 2001).

EP300 (p300) is SUMOylated at lysine-1020 and lysine-1024 with SUMO1 (Girdwood et al. 2003). SUMOylation of EP300 alleviates transcriptional repression caused by the CRD1 domain.

HIPK2 can simultaneously phosphorylate RUNX1 and EP300 (p300) histone acetyltransferase bound to the RUNX1:CBFB complex. RUNX1 is phosphorylated by HIPK2 at serine residues S249 and S273 and threonine residue T276. EP300 is phosphorylated by HIPK2 at multiple serine and threonine residues that have not been thoroughly identified. HIPK2-mediated phosphorylation contributed to the activation of histone acetyltransferase activity of EP300 at RUNX1 target promoters (Aikawa et al. 2006, Wee et al. 2008).

EP300 (p300) histone acetyltransferase acetylates RUNX3 on lysine residues K94 and K171 (Lee et al. 2013), and probably other lysines (Jin et al. 2004). EP300-mediated acetylation of RUNX3 is positively regulated by TGF-beta treatment. Besides increasing the transcriptional activity of RUNX3, EP300-mediated acetylation also increases the half-life of RUNX3, as it interferes with SMURF-mediated ubiquitination and subsequent degradation of RUNX3 (Jin et al. 2004).

The complex of CBFB and RUNX1 can bind histone acetyltransferase EP300 (p300). Formation of this complex does not depend on HIPK2-mediated phosphorylation of RUNX1. Histone acetyltransferase activity of EP300 probably contributes to transcriptional activation of RUNX1:CBFB target genes (Aikawa et al. 2006, Wee et al. 2008).

As inferred from mouse, RORA binds ROR elements (ROREs) in DNA and recruits the coactivators PPARGC1A (PGC-1alpha) and p300 (EP300, a histone acetylase) to activate transcription.

Under conditions of cellular stress, nuclear levels of phosphatidylinositol-5-phosphate (PI5P) increase and, through interaction with ING2, result in nuclear retention/accumulation of ING2. ING2 binds TP53 (p53) and recruits histone acetyltransferase EP300 (p300) to TP53, leading to TP53 acetylation. Increased nuclear PI5P levels positively regulate TP53 acetylation (Ciruela et al. 2000, Gozani et al. 2003, Jones et al. 2006, Zou et al. 2007, Bultsma et al. 2010).

Acetylation of RUNX3 by the histone acetyl transferase p300 (EP300) and the subsequent association of acetylated RUNX3 with BRD2 correlates with upregulation of p14-ARF transcription from the CDKN2A locus. Cyclin D1 (CCND1) negatively regulates RUNX3-facilitated induction of p14-ARF by recruiting histone deacetylase HDAC4 to RUNX3, leading to RUNX3 deacetylation (Lee et al. 2013).

In the nucleus, NICD2 forms a complex with RBPJ (CBF1, CSL) and MAML (mastermind). NICD2:RBPJ:MAML complex activates transcription from RBPJ-binding promoter elements (RBEs) (Wu et al. 2000). Besides NICD2, RBPJ and MAML, NOTCH2 coactivator complex likely includes other proteins, shown as components of the NOTCH1 coactivator complex.

NOTCH2 coactivator complex directly stimulates transcription of HES1 and HES5 genes (Shimizu et al. 2002), both of which are known NOTCH1 targets.

The promoter of FCER2 (CD23A) contains several RBEs that are occupied by NOTCH2 but not NOTCH1 coactivator complexes, and NOTCH2 activation stimulates FCER2 transcription. Overexpression of FCER2 (CD23A) is a hallmark of B-cell chronic lymphocytic leukemia (B-CLL) and correlates with the malfunction of apoptosis, which is thought be an underlying mechanism of B-CLL development. The Epstein-Barr virus protein EBNA2 can also activate FCER2 transcription through RBEs, possibly by mimicking NOTCH2 signaling (Hubmann et al. 2002).

NOTCH2 coactivator complex occupies the proximal RBE of the GZMB (granzyme B) promoter and at the same time interacts with phosphorylated CREB1, bound to an adjacent CRE site. EP300 transcriptional coactivator is also recruited to this complex through association with CREB1 (Maekawa et al. 2008). NOTCH2 coactivator complex together with CREBP1 and EP300 stimulates transcription of GZMB (granzyme B), which is important for the cytotoxic function of CD8+ T-cells (Maekawa et al. 2008).

There are indications that NOTCH2 genetically interacts with hepatocyte nuclear factor 1-beta (HNF1B) in kidney development (Massa et al. 2013, Heliot et al. 2013) and with hepatocyte nuclear factor 6 (HNF6) in bile duct formation (Vanderpool et al. 2012), but the exact nature of these genetic interactions has not been defined.

The transcriptional activity of the RUNX1:CBFB complex is regulated by interaction with co-factors and posttranslational modifications of RUNX1. Protein serine/threonine kinase HIPK2 can phosphorylate RUNX1 and affect transcriptional activity of the RUNX1:CBFB complex during hematopoiesis. Some CBFB mutations found in leukemia interfere with HIPK2-mediated phosphorylation of RUNX1. HIPK2 can simultaneously phosphorylate RUNX1 and EP300 (p300) bound to the RUNX1:CBFB1 complex (Aikawa et al. 2006, Wee et al. 2008).
The RUNX1:CBFB complex can associate with the polycomb repressor complex 1 (PRC1). PRC1 complexes are found at many RUNX1 target promoters and can act either as co-activators or co-repressors in the transactivation of RUNX1 targets (Yu et al. 2011).
RUNX1 recruits the SWI/SNF chromatin remodeling complex to many RUNX1 target promoters by directly interacting with several SWI/SNF subunits (Bakshi et al. 2010).
Other co-factors of the RUNX1:CBFB complex are annotated in the context of transcriptional regulation of specific genes.

Histone acetyltransferase p300