MAF functions as a pioneer transcription factor that initiates and sustains myelomagenesis
Journal article
Katsarou, A., Trasanidis, N., Ponnusamy, K., Kostopoulos, I., Alvarez-Benayas, J., Papaleonidopoulou, F., Keren, K., Sabbattini, P.M. R., Feldhahn, N., Papaioannou, M., Hatjiharissi, E., Sudbery, I., Chaidos, A., Caputo, V. and Karadimitris, A. (2023). MAF functions as a pioneer transcription factor that initiates and sustains myelomagenesis. Blood Advances. 7 (21), pp. 6395-6410. https://doi.org/10.1182/bloodadvances.2023009772
Authors | Katsarou, A., Trasanidis, N., Ponnusamy, K., Kostopoulos, I., Alvarez-Benayas, J., Papaleonidopoulou, F., Keren, K., Sabbattini, P.M. R., Feldhahn, N., Papaioannou, M., Hatjiharissi, E., Sudbery, I., Chaidos, A., Caputo, V. and Karadimitris, A. |
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Abstract | Deregulated expression of lineage-affiliated transcription factors (TFs) is a major mechanism of oncogenesis. However, how the deregulation of nonlineage affiliated TF affects chromatin to initiate oncogenic transcriptional programs is not well-known. To address this, we studied the chromatin effects imposed by oncogenic MAF as the cancer-initiating driver in the plasma cell cancer multiple myeloma. We found that the ectopically expressed MAF endows myeloma plasma cells with migratory and proliferative transcriptional potential. This potential is regulated by the activation of enhancers and superenhancers, previously inactive in healthy B cells and plasma cells, and the cooperation of MAF with the plasma cell-defining TF IRF4. Forced ectopic MAF expression confirms the de novo ability of oncogenic MAF to convert transcriptionally inert chromatin to active chromatin with the features of superenhancers, leading to the activation of the MAF-specific oncogenic transcriptome and the acquisition of cancer-related cellular phenotypes such as CCR1-dependent cell migration. These findings establish oncogenic MAF as a pioneer transcription factor that can initiate as well as sustain oncogenic transcriptomes and cancer phenotypes. However, despite its pioneer function, myeloma cells remain MAF-dependent, thus validating oncogenic MAF as a therapeutic target that would be able to circumvent the challenges of subsequent genetic diversification driving disease relapse and drug resistance. |
Keywords | Hematology |
Year | 2023 |
Journal | Blood Advances |
Journal citation | 7 (21), pp. 6395-6410 |
Publisher | American Society of Hematology |
ISSN | 2473-9529 |
2473-9537 | |
Digital Object Identifier (DOI) | https://doi.org/10.1182/bloodadvances.2023009772 |
Web address (URL) | https://ashpublications.org/bloodadvances/article/doi/10.1182/bloodadvances.2023009772/496007/MAF-functions-as-a-pioneer-transcription-factor |
Publication dates | |
25 Oct 2023 | |
Publication process dates | |
Accepted | 05 May 2023 |
Deposited | 21 Nov 2023 |
Publisher's version | License File Access Level Open |
Accepted author manuscript | License File Access Level Controlled |
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https://openresearch.lsbu.ac.uk/item/950w6
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