Table 1. Clusters and their associated GO terms and enriched TF-binding motifs.
| Cluster number and receptor sites (and cells) | Associated GO terms | Enriched TF-binding motifs |
|---|---|---|
| Cluster 1ERα (α cells) | Gene associated in ER+ tumors, downregulated in Tam-resistant tumorsAbnormal cell migration, mammary gland epithelium developmentEpithelial cell proliferationMammary gland development | ER, GATA3 (C1c)FOXA1, other FOX family members (C1b–c) |
| Cluster 2ERα (α,α/β)ERβ (β) | Mammary gland developmentAbnormal lactation, mammary gland, liver, and thymus developmentGene downregulated in tamoxifen-resistant breast cancers | ER |
| Cluster 3ERα (α/β)ERβ (β) | Mammary gland alveolar hyperplasiaIncreased cell proliferationEpithelial cell developmentMammary gland epithelium developmentFOXA1 TF network | ER |
| Cluster 4ERα (α,α/β)ERβ (α/β,β)SRC3 (α,α/β,β)RIP140 (α,α/β,β) | Epithelial cell differentiationMammary gland branchingGenes associated with tamoxifen resistance in breast tumors | ER, AP2α, Zic1, VDR |
| Cluster 5ERα (α,α/β)ERβ (α/β,β)SRC3 (α/β,β)RIP140 (β) | Fatty acid metabolismRegulation of NF-κB activityLiver inflammationIGF-1 signaling pathway | ER, AP2α, Snail, SP1 |
| Cluster 6ERα (α,α/β)ERβ (α/β,β) | PI3K bindingEpithelial cell proliferationProstate gland developmentFocal adhesionEndometrial carcinoma | ER, HNF4, AP1 |
| Cluster 7ERα (α,α/β)ERβ (α/β,β)RIP140 (β) | Cellular response to E2Adipose tissue developmentInsulin receptor subunit bindingMammary gland epithelia development | ER, Nurr, ROR, COUP-TF, HNF4 |
| Cluster 8ERβ (β) | Ubiquitin conjugating enzymesCell cycle and apoptosis | ER, E2F, ETS, CREB |
| Cluster 9ERβ (α/β) | Mammary gland alveolus developmentMammary gland epithelial cell proliferationIncrease cell proliferation | ER, AP2α, STAT3, p300, PAX-4 |
| Cluster 10ERβ (β) | Osteoblast developmentMammary gland epithelial developmentResponse to corticosteronep38 signaling pathway | ER, Snail, E2F |
| Cluster 11ERβ (β) | Apoptosis signaling pathwayCell proliferationGenes decreased during metastasisp38 signaling | ER, AP2α, SP1, ERR, LMO2, Hairy |
Web-based GREAT software was used to determine the GO grouping of genes that map to each cluster (20 kb window). Cistrome, Seqpos, and CEAS softwares were utilized to determine enriched TF-binding motifs.