Signatures of activators and repressors 2-2 22 2-2 22 TF Expression TF Expression 2-4 24 2-4 24 Motif enrichment Motif enrichment Motif enriched when TF is expressed Motif depleted when TF is expressed Active regions Repressed regions

Signatures of +/- TF regulators: CREB / HNF 0: “Off” state 5,6: “Enhancer” states 9: “On” state Repressor signature (CREB): When TF is expressed, motif is: Enriched in “off” states, Depleted in “on” states 0: “Off” state 5,6: “Enhancer” states 9: “On” state Activator signature (HNF): When TF is expressed, motif is: Enriched in “on” states, Depleted in “off” states 2-2 22 Expression 2-4 24 Fold enrichment

Another activator: STAT 0: “Off” state 5,6: “Enhancer” states 9: “On” state 2-2 22 Expression 2-4 24 Fold enrichment STAT: “Signal transducers and activator of transcription” We see different enrichment and expression for both GM12878 and K562 lines with STAT1/5 in both enhancer and “on” states

Signatures of activators and repressors Active states 2-2 22 TF Expression +TF expressed  Motif depleted 2-4 24 Motif enrichment Repressed states TF expr  no motif If motif  No expr 2-2 22 TF Expression Activator signature + 2-4 24 Motif enrichment +TF expressed  Motif enriched 2-2 22 TF Expression Repressed states -TF expressed  Motif enriched 2-4 24 Motif enrichment - 2-2 22 TF Expression Active states 2-4 24 Motif enrichment -TF expressed  Motif depleted TF expr  no motif If motif  No expr Repressor signature

Example of activator and repressor xx 0: “Off” state 5,6: “Enhancer” states 9: “On” state HNF HepG2 activator xx 0: “Off” state 5,6: “Enhancer” states 9: “On” state CREB GM repressor 2-2 22 Expression 2-4 24 Fold enrichment