Selection of a pathway of differentiation in multipotent progenitor cells may depend on the amount of histone H1 or H1 degrees relative to the core histones, With low levels of these linker histones, it is proposed that an evolutionarily more ancient cell differentiation occurs. Greater repetition of AT-rich regulatory motifs allows more frequent, hence earlier, transcription of genes, accounting for this type of cell differentiation. It is further proposed that a decrease of total cell protein accumulation leads to an increase of histone H1 or H1 degrees relative to the core histones. It is suggested that these linker histones preferentially bind the more AT-rich regulatory sequences, thereby restricting the phylogenetically more ancient differentiation potency. This allows differentiation of an evolutionarily younger cell type. BioEssays 21:333-338, 1999. (C) 1999 John Wiley & Sons, Inc.