REGULATION OF 3-D CHROMATIN ARCHITECTURE OF EMBRYONIC STEM CELLS

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Embryonic stem cells (ESCs) provide an experimentally tractable system to study developmentally regulated alterations in chromatin structure. ESCs are regarded as a potential source of material for stem cell therapies because they are pluripotent, or have the ability to differentiate into all cell types, and can grow indefinitely in the pluripotent state[14]. However, the molecular mechanisms governing self-renewal and pluripotency are not well understood. Work from many labs, including our own, shows that chromatin regulatory proteins play an important role in ESC self-renewal and pluripotency. ESCs are characterized by higher order chromatin structure that is generally dynamic and permissive to the transcriptional machinery. Genome-wide mapping of DNA methylation profiles and of post-translational histone modifications showed that specialized chromatin states characterize promoters of active, repressed and potentially active genes in ESCs. In addition, the same chromatin regulatory complex can have a very different role in ESCs than in somatic cells. In some instances, complexes that are essential in somatic cells are dispensable in ESCs: the Polycomb Repressive Complexes (PRCs) provide such an example.