Master Regulator Yields Big Surprises

In the textbooks, genes are controlled by transcription factors, proteins that bind to DNA near the starts of genes to activate or repress them. One of the best-studied transcription factors, called MyoD, is a master regulator of myogenesis, the process by which precursor cells differentiate into skeletal muscle cells. Indeed, expressing this one protein in a fibroblast (skin cell) causes extensive remodeling of the cell, resulting in a facsimile of a muscle cell. Walter L. Ruzzo and collaborators at the Fred Hutchinson Cancer Research Center have assayed genome-wide MyoD binding in differentiating and mature muscle cells, adding greatly to our understanding of these processes. They used "ChIP-seq" technology -- Chromatin ImmunoPrecipitation followed by next-gen sequencing. As expected, MyoD is found near start sites of the several hundred genes that are known to be driven by this powerful regulator. Surprisingly, however, these sites comprise only a tiny fraction of the sites bound by MyoD, many thousands of which occur far from any gene. These data suggest that MyoD is unexpectedly multifunctional, initiating changes in chromatin state that result in broad "reprogramming" of the cell, in addition to its canonical role in activating genes immediately adjacent to some of its target sites. Read the full article or the short accompanying comment in Developmental Cell, both cited below.