Table 1.
Examples of Coactivators and Corepressors That Regulate the ER-Driven Transcriptional Program
| Factors | General function | Reported ER-specific function | Refs |
|---|---|---|---|
| Coactivators | |||
| p300/CBP | Histone acetyltransferase (HAT) mediating histone acetylation, importantly on H3K27, modification found at active gene regulatory elements | Forms core complex with ER and is required for enhancer activity and target gene expression | (66, 67) |
| SRC1/2/3 | P160/nuclear receptor coactivator (NCoA) family. Possesses p300/CBP interaction domain and weak HAT activity | Forms core complex with ER and mediates the interaction between p300 and ER | (68, 69) |
| BRG1 | ATPase subunit in the SWI/SNF chromatin remodeling complex | Directly interacts with ER and is required for efficient ER-driven transcriptional activation | (70) |
| CARM1 | Arginine methyltransferase with activity toward histone and nonhistone substrates | Involved in both estrogen-induced activation and repression of genes; implicated in tamoxifen-resistant/ligand-independent activation of ER | (71, 72) |
| TET2 | Active DNA demethylation activity | Binds active enhancers and facilitates the recruitment and function of ER | (73) |
| Corepressors | |||
| CoREST | Complex with repressor activity and a subunit composition including HDACs, the lysine demethylase KDM1A/LSD1, and REST corepressor (RCOR) proteins | Transcriptional repressor for ligand-activated ER; CoREST subunits identified as required for gene regulation by ER and for ER-mediated cell growth | (74) |
| NCoR & SMRT | Transcriptional corepressors forming large assemblies which include HDAC activity | Associated with estrogen-suppressed genes and SERM-mediated response | (75, 76) |
| ARID1A | BAF chromatin remodeling complex; reported tumor suppressor gene implicated in various cancers | Recruited during tamoxifen treatment; mediates tamoxifen and fulvestrant response | (77, 78) |
| NuRD | Chromatin remodeling and HDAC complex | Associated with tamoxifen-induced recruitment | (74, 79-88) |
| Polycomb group proteins | Transcriptional repressors of developmental regulatory loci | Diverse links with ER biology reported; BMI1 & EZH2 associated with tamoxifen resistance, while RING1B linked with estrogen-driven gene activation | (89-92) |
List of coregulators discussed in the text, with a description of their general function and reported role in ER biology (list is not exhaustive and multiple other factors have been described to play a role in hormone-dependent signaling). The 3 factors we discuss in greater detail are shown in bold. References used in the main text relevant to their reported role in ER-bound enhancer functionality are included.
Abbreviations: ARID1A, AT rich interactive domain 1A; ER, estrogen receptor alpha; HAT, histone acetyltransferase; HDAC, histone deacetylase; NCoA, nuclear receptor coactivator; NuRD, nucleosome remodeling and deacetylase; SERM, selective estrogen receptor modulator.