Histone chaperone ASF1A accelerates chronic myeloid leukemia blast crisis by activating Notch signaling

Yin, Xiaolin; Zhou, Minran; Zhang, Lu; Fu, Yue; Xu, Man; Wang, Xiaoming; Cui, Zelong; Gao, Zhao; Li, Miao; Dong, Yuting; Feng, Huanqing; Ma, Sai; Chen, Chunyan

doi:10.1038/s41419-022-05234-5

Cited by 8 publications

(8 citation statements)

References 46 publications

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“…NOTCH proteome analysis in HT-29 colorectal carcinoma cells reveled no dimer specific preferred partner (Fig 6). Monomer preferred partners include ASF1A, a known Notch coactivator [39,40], MED12, MED9, PARP4 and TXNIP (Fig 6D), but since both proteins can exist in complexes as monomers, we did not explore these any further.…”

Section: Resultsmentioning

confidence: 99%

Notch dimerization contributes to maintenance of intestinal homeostasis by a mechanism involving HDAC2

Dai,

Preusse,

et al. 2024

Preprint

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A tri-protein complex containing NICD, RBPj and MAML1 binds DNA as monomer or, cooperatively, as dimers to regulate transcription. Mice expressing Notch dimerization-deficient (DD) alleles of Notch1 and Notch2 (NDD) are sensitized to environmental insults but otherwise develop and age normally. Transcriptomic analysis of colonic spheroids uncovered no evidence of dimer-dependent target gene miss-regulation, confirmed impaired stem cell maintenance in-vitro, and discovered an elevated signature of epithelial innate immune response to symbionts, the likely underlying cause for heightened sensitivity in NDD mice. TurboID followed by quantitative nano-spray MS/MS mass-spectrometry analyses in a human colon carcinoma cell line expressing either NOTCH2DD or NOTCH2 revealed an unbalanced interactome, with reduced interaction of NOTCH2DD with the transcription machinery but relatively preserved interaction with the HDAC2 interactome suggesting modulation via cooperativity. To ask if HDAC2 activity contributes to Notch loss-of-function phenotypes, we used the HDAC2 inhibitor Valproic acid (VPA) and discovered it could prevent the intestinal consequences of gamma secretase inhibitor (DBZ or DAPT) treatment in mice and spheroids, suggesting synergy between HDAC activity and pro-differentiation program in intestinal stem cells.

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Section: Resultsmentioning

confidence: 99%

Notch dimerization contributes to maintenance of intestinal homeostasis by a mechanism involving HDAC2

Dai,

Preusse,

et al. 2024

Preprint

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“…17 Histone demethylation is a key mechanism for epigenetic modification, of which dysregulation has an immeasurable effect on both TKI resistance and the transformation from CP CML to AP/BC CML. 18,19 Plant homeodomain finger protein 8 (PHF8) is a histone lysine demethylase with two active domains, plant homeodomain (PHD) and Jumonji C (JmjC). 20,21 PHF8 can demethylate H3K9me2/1, H4K20me1 and H3K27me2/1.…”

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confidence: 99%

Histone demethylase PHF8 facilitates the development of chronic myeloid leukaemia by directly targeting BCR::ABL1

Feng

Cui

et al. 2023

Br J Haematol

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SummaryAlthough tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of chronic myeloid leukaemia (CML), TKI resistance remains a major challenge. Here, we demonstrated that plant homeodomain finger protein 8 (PHF8), a histone demethylase was aberrantly enriched in CML samples compared to healthy controls. PHF8 inhibited CML cell differentiation and promoted CML cell proliferation. Furthermore, the proliferation‐inhibited function of PHF8‐knockdown have stronger effect on imatinib mesylate (IM)‐resistant CML cells. Mechanistically, we identified that PHF8 as a transcriptional modulator interacted with the promoter of the BCR::ABL1 fusion gene and alters the methylation levels of H3K9me1, H3K9me2 and H3K27me1, thereby promoting BCR::ABL1 transcription. Overall, our study suggests that targeting PHF8, which directly regulates BCR::ABL1 expression, is a useful therapeutic approach for CML.

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“…Additionally, ASF1A, the other replication‐coupled histone chaperone, was identified as an enhancer of differentiation arrest in chronic myeloid leukemia (CML) cells. Mechanistically, ASF1A was proposed to play an active role in initiating Notch signaling and upregulating H3K56 acetylation, which in turn resulted in CML acceleration and blast crisis 68 . Roles of H3.2 and CENP‐A in regulating hematopoiesis or driving hematological malignancy have not yet been described in literature.…”

Section: H3 Histones Have Specific Deposition Machineriesmentioning

confidence: 99%

Histone Variants and Their Chaperones in Hematological Malignancies

et al. 2023

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Epigenetic regulation occurs on the level of compacting DNA into chromatin. The functional unit of chromatin is the nucleosome, which consists of DNA wrapped around a core of histone proteins. While canonical histone proteins are incorporated into chromatin through a replication-coupled process, structural variants of histones, commonly named histone variants, are deposited into chromatin in a replication-independent manner. Specific chaperones and chromatin remodelers mediate the locus-specific deposition of histone variants. Although histone variants comprise one of the least understood layers of epigenetic regulation, it has been proposed that they play an essential role in directly regulating gene expression in health and disease. Here, we review the emerging evidence suggesting that histone variants have a role at different stages of hematopoiesis, with a particular focus on the histone variants H2A, H3, and H1. Moreover, we discuss the current knowledge on how the dysregulation of histone variants can contribute to hematopoietic malignancies.

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Histone chaperone ASF1A accelerates chronic myeloid leukemia blast crisis by activating Notch signaling

Cited by 8 publications

References 46 publications

Notch dimerization contributes to maintenance of intestinal homeostasis by a mechanism involving HDAC2

Notch dimerization contributes to maintenance of intestinal homeostasis by a mechanism involving HDAC2

Histone demethylase PHF8 facilitates the development of chronic myeloid leukaemia by directly targeting BCR::ABL1

Histone Variants and Their Chaperones in Hematological Malignancies

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