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Citations to this article

Disrupting the DREAM transcriptional repressor complex induces apolipoprotein overexpression and systemic amyloidosis in mice
Pirunthan Perampalam, … , Vathany Kulasingam, Frederick A. Dick
Pirunthan Perampalam, … , Vathany Kulasingam, Frederick A. Dick
Published January 14, 2021
Citation Information: J Clin Invest. 2021;131(4):e140903. https://doi.org/10.1172/JCI140903.
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Research Article Nephrology Vascular biology Article has an altmetric score of 2

Disrupting the DREAM transcriptional repressor complex induces apolipoprotein overexpression and systemic amyloidosis in mice

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Abstract

DREAM (Dp, Rb-like, E2F, and MuvB) is a transcriptional repressor complex that regulates cell proliferation, and its loss causes neonatal lethality in mice. To investigate DREAM function in adult mice, we used an assembly-defective p107 protein and conditional deletion of its redundant family member p130. In the absence of DREAM assembly, mice displayed shortened survival characterized by systemic amyloidosis but no evidence of excessive cellular proliferation. Amyloid deposits were found in the heart, liver, spleen, and kidneys but not the brain or bone marrow. Using laser-capture microdissection followed by mass spectrometry, we identified apolipoproteins as the most abundant components of amyloids. Intriguingly, apoA-IV was the most detected amyloidogenic protein in amyloid deposits, suggesting apoA-IV amyloidosis (AApoAIV). AApoAIV is a recently described form, whereby WT apoA-IV has been shown to predominate in amyloid plaques. We determined by ChIP that DREAM directly regulated Apoa4 and that the histone variant H2AZ was reduced from the Apoa4 gene body in DREAM’s absence, leading to overexpression. Collectively, we describe a mechanism by which epigenetic misregulation causes apolipoprotein overexpression and amyloidosis, potentially explaining the origins of nongenetic amyloid subtypes.

Authors

Pirunthan Perampalam, Haider M. Hassan, Grace E. Lilly, Daniel T. Passos, Joseph Torchia, Patti K. Kiser, Andrea Bozovic, Vathany Kulasingam, Frederick A. Dick

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Total citations by year

Year: 2025 2024 2023 2022 2021 Total
Citations: 1 2 1 2 1 7
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Citations to this article in year 2023 (1)

Title and authors Publication Year
Integration of transcriptomes of senescent cell models with multi-tissue patient samples reveals reduced COL6A3 as an inducer of senescence.
Savić R, Yang J, Koplev S, An MC, Patel PL, O'Brien RN, Dubose BN, Dodatko T, Rogatsky E, Sukhavasi K, Ermel R, Ruusalepp A, Houten SM, Kovacic JC, Stewart AF, Yohn CB, Schadt EE, Laberge RM, Björkegren JLM, Tu Z, Argmann C
Cell Reports 2023

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ISSN: 0021-9738 (print), 1558-8238 (online)

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