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PHF10 subunit of PBAF complex mediates transcriptional activation by MYC

Oncogene volume 40, pages 6071–6080 (2021)Cite this article

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Abstract

The PBAF complex, a member of SWI/SNF family of chromatin remodelers, plays an essential role in transcriptional regulation. We revealed a disease progression associated elevation of PHF10 subunit of PBAF in clinical melanoma samples. In melanoma cell lines, PHF10 interacts with MYC and facilitates the recruitment of PBAF complex to target gene promoters, therefore, augmenting MYC transcriptional activation of genes involved in the cell cycle progression. Depletion of either PHF10 or MYC induced G1 accumulation and a senescence-like phenotype. Our data identify PHF10 as a pro-oncogenic mechanism and an essential novel link between chromatin remodeling and MYC-dependent gene transcription.

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Fig. 1: PHF10 mRNA expression (RSEM counts) in cutaneous melanoma.
Fig. 2: MYC interacts with PBAF complex in melanoma cells.
Fig. 3: Influence of PHF10 knockdown on MYC-PBAF interaction in A375 cells.
Fig. 4: MYC regions responsible for interaction with PHF10.
Fig. 5: PHF10 knockdown decreases MYC reporter transactivation in HEK293T cells.
Fig. 6: Depletion of PHF10 or MYC induces similar changes in global gene expression.
Fig. 7: PHF10 cooperates with MYC-dependent transcription in A375 melanoma cells.
Fig. 8: Role of PHF10 and MYC knockdown in senescence and cell cycle distribution in melanoma cells.
Fig. 9: MYC and PBAF cooperate in activation of genes involved in proliferation.

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Acknowledgements

We thank the Center for Precision Genome Editing and Genetic Technologies for Biomedicine (Institute of Gene Biology) supported by Ministry of Science and Higher Education of the Russian Federation (075-15-2019-1661) for providing the equipment.

Funding

This study was supported by the Russian Foundation of Basic Research (grant #17-54-33031 (to SGG) and NIH R21 CA220096 grant (to MAN).

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Authors and Affiliations

  1. Department of Eukaryotic Transcription Factors, Institute of Gene Biology, Russian Academy of Sciences, Moscow, Russia

    N. V. Soshnikova, E. V. Tatarskiy & S. G. Georgieva

  2. Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia

    N. V. Soshnikova

  3. Laboratory of Molecular Oncobiology, Institute of Gene Biology, Russian Academy of Sciences, Moscow, Russia

    V. V. Tatarskiy & A. A. Shtil

  4. Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Institute of Gene Biology, Russian Academy of Sciences, Moscow, Russia

    N. S. Klimenko

  5. Department of Cancer Biology, Wake Forest University, Winston-Salem, NC, USA

    M. A. Nikiforov

  6. Department of Transcription Factors, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia

    S. G. Georgieva

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  1. N. V. Soshnikova
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Contributions

Conceptualization: NVS, MAN, SGG, AAS; methodology: NVS, VVT, NSK, AAS; validation: VVT, EVT, NSK; investigation: NVS, EVT, NSK, VVT; resources: EVT, SGG; data curation: NVS, VVT, NSK; writing (original draft): NVS, SGG, AAS, NSK; writing (review and editing): NVS, SGG, AAS, MAN; visualization: NVS, VVT, EVT, NSK; supervision: SGG; project administration: NVS, SGG, MAN; funding acquisition: SGG, MAN.

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Correspondence to N. V. Soshnikova or S. G. Georgieva.

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Soshnikova, N.V., Tatarskiy, E.V., Tatarskiy, V.V. et al. PHF10 subunit of PBAF complex mediates transcriptional activation by MYC. Oncogene 40, 6071–6080 (2021). https://doi.org/10.1038/s41388-021-01994-0

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