Genome-wide mapping of chromatin state of mouse forelimbs

Background: Cell types are defined at the molecular level during embryogenesis by a process called pattern formation and created by the selective utilization of combinations of sequence-specific transcription factors. Developmental programs define the sets of genes that are available to each particular cell type, and real-time biochemical signaling interactions define the extent to which these sets are used at any given time and place. Gene expression is regulated through the integrated action of many cis -regulatory elements, including core promoters, enhancers, silencers, and insulators. The chromatin state in developing body parts provides a code to cellular populations that directs their cell fates. Chromatin profiling has been a method of choice for mapping regulatory sequences in cells that go through developmental transitions. Results: We used antibodies against histone H3 lysine 4 trimethylations, a modification associated with promoters and open/active chromatin, histone H3 lysine 27 trimethylations associated with Polycomb-repressed regions, and ribonucleic acid polymerase II associated with transcriptional initiation to identify the chromatin state signature of the mouse forelimb during mid-gestation at embryonic day 12. The families of genes marked included those related to transcriptional regulation and embryogenesis. One-third of the marked genes were transcriptionally active, whereas only a small fraction were bivalent marked. Sequence-specific transcription factors that were activated were involved in cell specification, including bone and muscle formation. Conclusion: Our results demonstrate that embryonic limb cells do not exhibit the plasticity of the embryonic stem cells but rather are programmed for a finer tuning for cell lineage specification.