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MLL4 mediates differentiation and tumor suppression through ferroptosis.

ABSTRACT: The epigenetic regulator, MLL4 (KMT2D), has been described as an essential gene in both humans and mice. In addition, it is one of the most commonly mutated genes in all of cancer biology. Here, we identify a critical role for Mll4 in the promotion of epidermal differentiation and ferroptosis, a key mechanism of tumor suppression. Mice lacking epidermal Mll4, but not the related enzyme Mll3 (Kmt2c), display features of impaired differentiation and human precancerous neoplasms, all of which progress with age. Mll4 deficiency profoundly alters epidermal gene expression and uniquely rewires the expression of key genes and markers of ferroptosis (Alox12, Alox12b, and Aloxe3). Beyond revealing a new mechanistic basis for Mll4-mediated tumor suppression, our data uncover a potentially much broader and general role for ferroptosis in the process of differentiation and skin homeostasis.

SUBMITTER: Egolf S

PROVIDER: S-EPMC8664260 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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MLL4 mediates differentiation and tumor suppression through ferroptosis.

Egolf Shaun S Zou Jonathan J Anderson Amy A Simpson Cory L CL Aubert Yann Y Prouty Stephen S Ge Kai K Seykora John T JT Capell Brian C BC

Science advances 20211210 50

The epigenetic regulator, MLL4 (KMT2D), has been described as an essential gene in both humans and mice. In addition, it is one of the most commonly mutated genes in all of cancer biology. Here, we identify a critical role for Mll4 in the promotion of epidermal differentiation and ferroptosis, a key mechanism of tumor suppression. Mice lacking epidermal Mll4, but not the related enzyme Mll3 (Kmt2c), display features of impaired differentiation and human precanc ...[more]

PMID: 34890228

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MLL4 mediates differentiation and tumor suppression through ferroptosis.

Publications

MLL4 mediates differentiation and tumor suppression through ferroptosis.

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