Abstract
Dynamic structural properties of chromatin play an essential role in defining cell identity and function. Transcription factors and chromatin modifiers establish and maintain cell states through alteration of DNA accessibility and histone modifications. This activity is focused at both gene-proximal promoter regions and distally located regulatory elements. In the three-dimensional space of the nucleus, distal elements are localized in close physical proximity to the gene-proximal regulatory sequences through the formation of chromatin loops. These looping features in the genome are highly dynamic as embryonic stem cells differentiate and commit to specific lineages, and throughout reprogramming as differentiated cells reacquire pluripotency. Identifying these functional distal regulatory regions in the genome provides insight into the regulatory processes governing early mammalian development and guidance for improving the protocols that generate induced pluripotent cells.
Highlights
Mammalian development is a process that progressively alters cell plasticity as cells commit to their differentiated state
As previously mentioned, reprogramming somatic cells to induced pluripotent stem (iPS) cells was first accomplished by forced expression of a cocktail of four transcription factors, OSKM
Observations of whole nuclei reveal that the chromatin landscape of embryonic stem (ES) cells is a loosely packed mesh of fibers, with less condensed chromatin than that observed in somatic cells [26]
Summary
Mammalian development is a process that progressively alters cell plasticity as cells commit to their differentiated state These changes in cell state are accompanied by dynamic changes in the transcriptome, chromatin properties and nuclear organization of the genome. Repositioning of gene loci within the nuclear space and altered configuration of entire chromosomes occur as ES cells differentiate and somatic cells undergo reprogramming. Despite these changes, some architectural features of genome organization appear to be more universal and are. We discuss the dynamic features of chromatin and genome topology in the context of lineage commitment and cellular reprogramming and highlight emerging mechanisms controlling the concomitant changes in cellular phenotypes
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