CELL FATE DETERMINATION IN 3D: REGULATION OF GENE EXPRESSION VIA CHROMATIN INTERACTIONS WITH THE NUCLEAR MEMBRANE.

In the nucleus of all cells, DNA is packaged in association with histone proteins to form chromatin. It is becoming increasingly clear that the organization of chromatin in three dimensions within the nucleus is highly regulated and can contribute to gene expression and cell function. The regions of the genome that are near the nuclear periphery are termed "lamin associated domains" or LADs (1-3). Here, I present a theory, based on recent results, for "chromatin competence" in which the organization of LADs in a progenitor cell accounts for the ability of that cell to respond to external factors to promote differentiation into one lineage or another. I propose that a cell can only respond to an inductive cue if the downstream genes are available for activation, and that genes are not available for activation if they are sequestered in LADs.