Figure 8.

LHX2 binding at Fezf2 and Sox11 recruits NuRD subunits. (A) Scheme depicts Lhx2 binding to distal enhancers of the target genes Fezf2 and Sox11. Lhx2 recruits repressive NuRD subunits and becomes juxtaposed to the transcription start site via chromatin looping. Consequently, transcription of Fezf2 and Sox11 is reduced with only few active histone marks (green lollipops) at the enhancer and transcription start site. Superficial layer neurons retain Lhx2 expression from their birth date through maturity, thus preventing subcerebral identity, while neurons of deep layer 5 and 6 rapidly repress Lhx2 expression, thus favoring subcerebral identity. (B) Cortex-specific Lhx2 knockout mice show derepression of Fezf2 and Sox11with an increase in active histone marks. This leads to a strong increase in layer 5 neurons expressing high levels of Fezf2 and Ctip2, indicating subcerebral fate. Model adapted from Muralidharan et al. (2017), attribution CC BY.