Supplementary Figure 7: A model for mechanisms by which mutant Huntingtin influences the selection and activation of microglia enhancers.
From: Mutant Huntingtin promotes autonomous microglia activation via myeloid lineage-determining factors
Left: PU.1 and C/EBPs function in a collaborative manner to select microglia enhancers from inactive chromatin in basal conditions. Pro-inflammatory signals that activate transcription factors such as the p65 component of NFκB lead to inflammatory response. Right: mutant Huntingtin expression enhances this process by increasing PU.1 expression and PU.1-C/EBPs promoter binding, leading to increased enhancer activity under basal conditions that results in increased basal pro-inflammatory and neurotoxic genes expression. This phenomenon increases the sensitivity to pro-inflammatory signals. In fact, under conditions of sterile inflammation mutant Huntingtin-expressing microglia appears to be more efficient in inducing neuronal death.
