Functional categories described as having housekeeping functions, such as translational elongation, or components of the ATP-generating proton pump had a much greater fraction of active loci in pluripotent cells, and few of these loci changed state during differentiation. Loci annotated for functions in later mesodermal derivatives, like regulation of heart contraction had a high percentage that were transcriptionally paused during pluripotency and were transcriptionally activated in mesoderm. Conversely, loci annotated for functionality in ectodermal derivatives such as neurotransmitter receptor activity or keratinization tended to start as paused in pluripotent cells, and then were archived to a silent state in mesoderm. This is consistent with ectodermal derivatives being U0126 strongly suppressed in our directed differentiation system. Significantly, ontologies with developmentally relevant functions were more likely to contain paused genes becoming both active and silent during differentiation. We hypothesized that, by focusing on genes that were transcriptionally paused in embryonic stem cells and changed state during commitment to mesoderm, we could predict the later cardiomyocyte fate of the population. Consistent with the future fate of the mesodermal cell population, genes annotated for ectodermal ontologies of neurotransmitter receptor activity, keratinization and brain development have high percentages that lose initiation and are thus archived away. Conversely, the loci of genes in the cardiovascular mesoderm ontologies of heart development, blood vessel development, heart looping and regulation of heart contraction have high percentages that proceed to full-length transcription. By observing how loci exit from paused transcription early in differentiation, we get a strong prediction of future cell fate commitment, one that would not be available through conventional array analysis alone. The paused state of transcription seems to play a central role in the change of gene expression during the differentiation of pluripotent human embryonic stem cells. By using a directed differentiation system, along with closely spaced temporal resolution, here we were able to observe that transcriptional initiation without elongation is a key transition state for loci undergoing activation or silencing. In our system, as cells commit to mesodermal lineages from pluripotency, we demonstrated that loci changing state seldom gain or lose initiation and elongation together. Rather, these two steps are decoupled, and apparently distinctly regulated. A small subset of genes appeared to move directly from fully active to fully silent and vice-versa, but it is possible that these genes moved through the paused state more quickly than our 2-day resolution could detect. Several studies have recently shed light into the molecular regulation of transcriptional pausing.