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“The opposing transcriptional functions of Sin3A and c-Myc are required to maintain skin homeostasis”

July 15, 2011 @ 4:00 pm - January 29, 2022 @ 4:54 am

The proto-oncogene c-Myc has emerged as an important stem cell regulator, yet it is largely unknown how c-Myc mechanistically balances self-renewal, proliferation and differentiation processes in adult tissues. Here, we explored the transcriptional roles of c-Myc at the Epidermal Differentiation Complex (EDC), a locus essential for skin maturation. Binding of c-Myc to EDC genes can simultaneously recruit or displace specific sets of differentiation-specific transcriptional regulators, including Klf4 and Ovol-1 or C/EBPα and Sin3A respectively. In this network, we identify Sin3A as a direct repressor of c-Myc activity via de-acetylation of the c-Myc protein. In the absence of Sin3A, genomic recruitment c-Myc to the EDC is enhanced and re-activation of Myc-target genes drive aberrant epidermal proliferation and differentiation. Simultaneous deletion of c-Myc and Sin3A reverts the skin phenotype to normal. In summary, we identify how the balance of two transcriptional key regulators can maintain tissue homeostasis via a negative feedback loop.

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Start:
July 15, 2011 @ 4:00 pm
End:
January 29, 2022 @ 4:54 am
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Venue

Seminar Room, Center for Molecular Medicine, Cologne
Seminar Room, Center for Molecular Medicine, Cologne, + Google Map

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