Cell-type specific cis -regulatory networks

Abstract

H ox proteins are a prominent class of transcription factors that spec- ify cell and tissue identities in animal embryos. In sharp contrast to tissue- specifically expressed transcription fac- tors, which coordinate regulatory path- ways leading to the differentiation of a selected tissue, Hox proteins are active in many different cell types but are nonetheless able to differentially regu- late gene expression in a context-depen- dent manner. This particular feature makes Hox proteins ideal candidates for elucidating the mechanisms employed by transcription factors to achieve tis- sue-specific functions in multi-cellular organisms. Here we discuss how the recent genome-wide identification and characterization of Hox cis-regulatory elements has provided insight concern- ing the molecular mechanisms underly- ing the high spatiotemporal specificity of Hox proteins. In particular, it was shown that Hox transcriptional outputs depend on the cell-type specific inter- play of the different Hox proteins with co-regulatory factors as well as with epigenetic modifiers. Based on these observations it becomes clear that cell- type specific approaches are required for dissecting the tissue-specific Hox regu- latory code. Identification and com- parative analysis of Hox cis-regulatory elements driving target gene expression in different cell types in combination with analyses on how cofactors, epi- genetic modifiers and protein-protein interactions mediate context-depen- dent Hox function will elucidate the mechanistic basis of tissue-specific gene regulation.