be230cLecture6

7 41813 dna methylakon pluripotency genes in somakc

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Unformatted text preview: NonFermentable) complex of ~11 proteins including catalyKc Brahma subunits (either Brg or Brm) and many non ­catalyKc structural subunits known as Brahma ­associated factors (BAFs) –  Open and maintain acKve state of pluripotent genes –  Oppose the Polycomb Repressive Complex (PRC) •  Other chormaKn remodelling complexes are also elevated and parKcipate in reprogramming, such as NuRD/Mi ­2/CHD – typically involved in repression but also maintain pluripotency. Histone ModificaKons •  AcetylaKon –  Histone acetyl transferases (HATs) acetylate histones and confer transcripKonal acKvity, and “open” chromaKn. –  Histone deacetylases (HDACs) deacetylate –  HDAC inhibitors, e.g. valproic acid, facilitate reprogramming •  MethylaKon –  ModificaKons to methylaKon pagern can alter propensity to reprogram, examples: –  Removing H3K4me3, which characterizes “acKve” chromaKn, causes differenKaKon (H3K4me3 can be removed with the Kdm1a demethylase) –  Increase in H3K9me3, which characterizes “silent” chromaKn blocks the effect of Oct4 and Nanog, e.g. loss of the Jmjd2 demethylase (increases H3K9me3) blocks reprogramming while overexpression increases reprogramming incidence. –  Recently, Daley lab showed that H3K79me3 (“acKve”) is lost duri...
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