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XB-IMG-154132

Xenbase Image ID: 154132

Fig. 6. Model displaying the mechanism by which c-Myc is paused in neural crest cells. On the left c-Myc is shown in a paused state with Pol ll bound to NELF, DSIF and Gdown1. We have shown that a knockdown of the P-TEFb components CDK9 and CYCLINT1 leads to a loss of c-Myc expression and a subsequent loss of Sox10 expression and incorrect development of neural crest derivatives (bottom scenario). This suggests in a wild type neural crest cell, P-TEFb is promoting transcriptional elongation of c-Myc. P-TEFb in its active form bound to the SEC will phosphorylate DSIF, NELF, Gdown1 and serine2 of the C terminal of RNA Pol ll. This promotes pause release on the c-Myc gene and allows the subsequent expression of Sox10 leading to correct synchronous development of neural crest derivatives (top scenario). S2=Serine2, S5=Serine5, P=phosphorylation mark, NELF=Negative elongation factor, DSIF=DRB sensitivity inducing factor, Pol ll=RNA polymerase II, CDK9=Cyclin dependent kinase 9, SEC=Super elongation complex.

Image published in: Hatch VL et al. (2016)

Copyright © 2016. Image reproduced with permission of the Publisher, Elsevier B. V.

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