Fig 7

Fig 7

Low affinity, widespread binding of MEIS (blue square) defines a large subset of accessible chromatin (grey line) for activation (PBX is not shown as PBX and MEIS binding almost entirely overlap). Direct cooperativity with HOX (A2 and A3, red and green circles respectively) and/or indirect cooperativity with tissue-specific TFs (triangle) increase MEIS binding affinity and residence time; prolonged residence time of MEIS at enhancers promotes recruitment of general co-activators (yellow) and activation of transcription. HOX paralogs preferentially bind different subsets of MEIS occupied regions, resulting in differential transcription. Three examples of BA-specific transcription are shown. In a, the red site is bound with higher affinity by HOXA2 than HOXA3, resulting in the formation of a more stable HOX-TALE complex on DNA and a (higher) transcriptional output in BA2. Conversely, in c, the green site is only recognized by HOXA3, leading to high affinity MEIS binding only in PBA, and to PBA-specific transcription. In b, the effect of HOXA3 is potentiated by a PBA-specific TF binding in the vicinity. Co-binding with tissue-specific TFs may positively contribute to HOX-MEIS cooperativity by competing with nucleosome for DNA binding, especially at HOX and/or MEIS low affinity sites. These mechanisms result in BA-specific transcription.