Red blood cell differentiation requires a stickier histone H1, which closes chromatin to transcription, based on findings from Dhananjay Yellajoshyula and David Brown (University of Mississippi, Jackson, MS). The less sticky form, however, might favor transcription not by falling off faster but by relaxing chromatin.

Undifferentiated cells need relaxed, accessible chromatin to keep their transcriptional options open. At their most pluripotent, stem cells contain a pool of highly mobile H1 that was thought to fall off easily and give way to transcription factors.

This H1 mobility, Brown finds, must be reined in during red blood cell maturation, to “shut down genes you don't need and leave on only the ones you do.” The crucial loss of mobility is gained by dephosphorylating H1. A mutant H1 that mimics the phosphorylated form blocked differentiation. It also boosted the mobility of its unphosphorylated counterpart—an effect that cannot easily be explained simply by its lower chromatin affinity.

Although mobile, phosphorylated H1 was still retained in chromatin much of the time. “Maybe it doesn't depart,” says Brown, “but instead inhibits compaction.” The added positive charge of a phosphate might interfere with H1's ability to neutralize DNA's negative charge, thereby preventing chromatin from condensing as tightly. A more open structure, Brown proposes, might also affect the mobility of other factors, including unphosphorylated H1—potentially spreading the altered structure.


Yellajoshyula, D., and D.T. Brown.
. Proc. Natl. Acad. Sci. USA. doi:.