A System for Genome-Wide Histone Variant Dynamics In ES Cells Reveals Dynamic MacroH2A2 Replacement at Promoters


The ability of cells to remember the correct cell fate is at least partly dependent on how the genome is packaged. Embryonic stem (ES) cells, which have the ability to become any cell type in the body, are a particularly well-studied system for understanding how the packaging of the genome – chromatin – controls cell state. One of the more curious aspects of ES cell chromatin is its “hyperdynamic” nature, as the histone proteins that comprise chromatin have been reported to exchange rapidly on and off the DNA in these cells. Here, we report a pulse chase system for studying histone dynamics in mouse ES cells, and report on the dynamics of two histone variants, H3.3 and MacroH2A2. Notably, MacroH2A2 is highly dynamic in ES cells, with rapid exchange occurring over gene promoters, alongside much more stably-bound domains that cover large blocks of the genome. Upon differentiation to fibroblasts MacroH2A2 becomes much more stably-bound to the genome, consistent with the idea that this histone variant plays a role in “locking down” repressed regions the genome. These results provide further evidence for a key role of histone dynamics in control of cell state inheritance.


Vyšlo v časopise: A System for Genome-Wide Histone Variant Dynamics In ES Cells Reveals Dynamic MacroH2A2 Replacement at Promoters. PLoS Genet 10(8): e32767. doi:10.1371/journal.pgen.1004515
Kategorie: Research Article
prolekare.web.journal.doi_sk: 10.1371/journal.pgen.1004515

Souhrn

The ability of cells to remember the correct cell fate is at least partly dependent on how the genome is packaged. Embryonic stem (ES) cells, which have the ability to become any cell type in the body, are a particularly well-studied system for understanding how the packaging of the genome – chromatin – controls cell state. One of the more curious aspects of ES cell chromatin is its “hyperdynamic” nature, as the histone proteins that comprise chromatin have been reported to exchange rapidly on and off the DNA in these cells. Here, we report a pulse chase system for studying histone dynamics in mouse ES cells, and report on the dynamics of two histone variants, H3.3 and MacroH2A2. Notably, MacroH2A2 is highly dynamic in ES cells, with rapid exchange occurring over gene promoters, alongside much more stably-bound domains that cover large blocks of the genome. Upon differentiation to fibroblasts MacroH2A2 becomes much more stably-bound to the genome, consistent with the idea that this histone variant plays a role in “locking down” repressed regions the genome. These results provide further evidence for a key role of histone dynamics in control of cell state inheritance.


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Genetika Reprodukčná medicína

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