Module 4: Figure ETS activation
Gene activation through co-operation of the E twenty-six (ETS) and serum response factor (SRF) transcription factors.
A ternary complex is formed through DNA, the serum response factor (SRF) bound to the CArG box and the E twenty-six (ETS) transcription factors such as Elk-1, which bind to the ETS-binding site (EBS) on DNA and to SRF through their Pointed (PNT) domains. In the inactive state, as shown at the bottom, ETS functions as a repressor by recruiting inhibitors such as the histone deacetylases (HDACs), which deacylate histone to increase chromatin condensation. A major activator of transcription is the extracellular-signal-regulated kinase (ERK) pathway of the mitogen-activated protein kinase (MAPK) signalling pathway, with the effector ERK1/2 phosphorylating sites on the activation domain (AD). Just how this phosphorylation induces transcription is unclear, but there does appear to be an activation of histone acetyltransferases (HATs), such as p300, to increase histone acetylation to decondense the chromatin.