Table 1 Literature evidence supporting the roles of TFs and TF pairs, as predicted by GEMSTAT models

From: Mechanistic analysis of enhancer sequences in the estrogen receptor transcriptional program

TF

GEMSTAT inferred role

% enhancer affected

Avg. % change

Literature-suggested role for TF

Reference PMID

ERα

Strong activator

63.8

−32.5

Transcriptional activator

26884552

FOXA1

Weak activator

47.1

−20.0

Pioneer factor. Alters DNA accessibility profile and is necessary for Estrogen-induced ERα binding.

18358809,16009131, 21151129

NKX3-1

Weak inhibitor

22.4

16.0

Represses ERα activity by competitively binding to chromatin/recruiting HDAC1

18794125

NR5A2

Strong activator

26.7

−20.2

Activates ERα-mediated transcription at least partly through co-binding to Estrogen Response Elements.

22359603

PBX1

Weak activator

6.4

−24.7

Pioneer factor

22125492

PGR

Strong/Weak inhibitor

6.4

−9.2

Unclear/controversial

26153859,28729413, 27885264

RELA (NFκb)

Ambiguous (weak activator/strong inhibitor)

9.3

−13.1

Transcriptional activation; controversial since ERα is known to repress NFκb transcriptional activity

25752574,20705611, 19920189,18703630, 22963717

RUNX1

Weak activator/Strong binding

10.55

−6.75

Mediates indirect binding (tethered) of ER to DNA

20547749

SP1

Weak activator

18.8

−8.7

Transcriptional activation in part due to mediation of indirect ERα-DNA binding

9328340,11250935, 11345900

AP2-γ

Strong Activator

9.0

−12.8

Pioneer factor

21572391

YBX1

Weak/Strong inhibitor

9.8

10.1

Transcriptional repression through direct interaction with ERα

29180470

ERα:FOXA1

Cooperative

17.8

−17.7

Cooperative activity essential for ERα activity

18358809,16009131, 21151129

  1. “% enhancer affected” indicates the percent of enhancers affected by ≥5 percentile (ensemble average). “Avg. % change” represents the predicted percentile change in activity after knock-down, averaged over enhancers that were affected more than 5 percentile points. Note that only factors that affect more than 5% of the tested enhancers (i.e., % enhancer affected ≥5) are included in this table. Same information for all TFs and interactions is shown in Supplementary Table 2.