Fig. 5: A working model for the actions of SETD2 on nucleosomes. | Cell Discovery

Fig. 5: A working model for the actions of SETD2 on nucleosomes.

From: Cryo-EM structure of SETD2/Set2 methyltransferase bound to a nucleosome containing oncohistone mutations

Fig. 5

a In normal cells, SETD2/Set2 directly associates with RNA Pol II and implements H3K36 methylation on partially unwrapped nucleosomes, co-transcriptionally. After that, SETD2/Set2 is rapidly released from the nucleosomes, and the DNA wraps back to its canonical conformation. However, in cancer cells carrying the oncogenic H3.3K36M mutations, SETD2/Set2 is withheld on the H3.3K36M nucleosome, which impairs the normal functions of SETD2/Set2 and possibly affects the movement of RNA pol II during transcription elongation. b A schematic drawing shows that histone H1 stabilizes the compact conformation of the nucleosome and prohibits the binding of SETD2 on the nucleosome.

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