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. Author manuscript; available in PMC: 2020 Nov 1.
Published in final edited form as: J Mol Biol. 2019 Nov 2;432(6):1801–1815. doi: 10.1016/j.jmb.2019.10.021

Figure 3: Connecting the impact of 5mC on TF binding to distinct readout mechanisms.

Figure 3:

(A) An example 5mC effect size quantification is shown for the TF complex formed between the human Pbx1 and HoxA1 proteins (left). Both enhanced (pink) and reduced (green) binding are observed depending on the positioning of the methylated CpG within the protein-DNA interface. (B) Enhanced binding stems from a stabilizing VdW contact between the 5mC base at DNA position 9 and Ile-47 within helix-3 of the Hox homeodomain (“base readout”). (C) Reduced binding can be attributed to a widening of the DNA minor groove at the consensus AY base step that directly neighbors the methylated C6G7. The MGW readout of the N-terminal arm of the Hox homeodomain is weakened as a result (“shape readout”).