be230cLecture6

Heterochromakn darker and closed is relakvely sparse

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Unformatted text preview: is state probably reflects the acKvity of certain transcripKon factors in parKcular lineages (in addiKon to pluripotency). B.  The metastable state can give rise to parKally reprogrammed cells, or even to differenKated lineages with the correct lineage ­specific transcripKon factors. C.  The probabilisKc events eventually decline, but can culminate in the stable inducKon of Sox2, which iniKates a determinisKc transiKon to the pluripotent state. InducKon of Nanog is a hallmark of this later step and acquisiKon of pluripotency. Fig. 3. Nuclei enlarge and chromatin decondenses during nuclear reprogramming. J B Gurdon, and D A Melton Science 2008;322:1811-1815 Published by AAAS AcetylaKon and MethylaKon ModificaKons Type of modification monomethylation dimethylation trimethylation acetylation H3K4 H3K9 H3K14 activation[22] activation[23] repression[25] activation[26] repression[23] Histone H3K27 H3K79 H4K20 H2BK5 activation[23] activation[23][24] activation[23] activation[23] repression[25] activation[24] repression[23] activation,[24] repression[23] repression[25] activation[26] activation[26] 6 4/18/13 EpigeneKc PerspecKve •  ESCs typically contain large amounts of euchromaKn (which is lighter staining and has an “open” configuraKon) relaKve to somaKc cells. HeterochromaKn (darker and “closed”) is relaKvely sparse in ESCs. This is similar to E3.5 mouse embryos. •  With somaKc cell reprogramming: –  Increase in euchromaKn, and rearrangement of heterochromaKn, as judged by H3K9me3, an epigeneKc mark of non ­transcribed DNA. –  The increase in euchromaKn precedes Nanog acKvaKon (marker of pluripotent state). –  Increase in H3K4me3 (open/acKve) along with no change in H3K27me3 (closed/inacKve). The two marks together indicate “poised” chromaKn. ChromaKn Remodelling •  ATP dependent chromaKn remodelling machinery: –  SWI/SNF (SWItch/Sucrose...
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