SOX after SOX: SOXession regulates neurogenesis

Abstract

Vertebrate embryonic stem (ES) cells give rise to many different cell types in multistep processes. These involve the establishment of a competent state, specification, differentiation, and maturation, and often involve Sox transcription factors. In this issue of Genes & Development, Bergsland and colleagues (pp. 2453-2464) determine the genome-wide binding profile of Sox2, Sox3, and Sox11 as ES cells become specified to neural precursors and differentiate into neurons. An ordered, sequential binding of these Sox proteins to a common set of gene enhancers was found to drive neurogenesis, as Sox proteins first help to preselect neural genes in ES cells and later ensure their proper activation in neural precursors or neurons.

Figure 1.

Relationship, expression, and activities of Sox factors involved in neurogenesis. (A) The Sox family tree with its various subgroups. Members are only listed for the SoxB1, SoxB2, and SoxC subgroups. (B) Summary of the findings by Bergsland et al. (2011). In ES cells, Sox2 binds ES cell-specific and neural enhancers. The ES cell-specific enhancers are marked by H3K4me3 and activated by Sox2, whereas the neural enhancers carry both H3K4me3 and H3K27me3 marks and are silent. Upon specification to NPCs, Sox2 may be replaced on neural enhancers by other SoxB1 proteins, such as Sox3. Neural enhancers bound by Sox2 or Sox3 (Sox2/3) are again either marked by H3K4me3 or carry both H3K4me3 and H3K27me3 marks. The former correspond to SoxB1-activated NPC enhancers, and the latter remain silent in NPCs. After neuronal differentiation, both types of enhancers exchange their SoxB1 factors for SoxC factors, including Sox11. The NPC enhancers acquire H3K27me3 and are inactive, whereas the previously poised enhancers with bivalent histone marks convert to a monovalent chromatin signature with H3K4me3 only and are active as neuronal enhancers.