Table 1 Comparison of features of wild-type DUX4 and DUX4-rearranged proteins.
From: DUX4-rearranged B-ALL: deciphering a biological and clinical conundrum
Feature | Wild-type DUX4 | DUX4-rearrangement |
|---|---|---|
Genetic Context | Encoded in the D4Z4 or 10q26 loci as a full-length transcript. | Involves rearrangement with IGH, ERG, or other gene partners. |
Protein Structure | Contains a full-length TAD. | Truncated TAD, often replaced by partner gene sequences. |
Transcriptional Activity | Pioneer factor, recruits p300/CBP for gene activation. | Not a pioneer factor, recruits RAG1/2, TCF12 and GTF2I for gene activation and alternative splicing |
Chromatin Impact | Induces H3K27Ac modifications at its binding sites. | Does not induce H3K27Ac or increase chromatin accessibility. |
Target Genes | Activates genes essential for early embryogenesis (e.g., ZSCAN4, DUXA, RFPL4A). | Activates genes related to cell adhesion, migration, and cancer metastasis (e.g., ERG, ITGA6, AGAP1). |
Expression Pattern | Transiently expressed in cleavage-stage embryos, germline cells and thymus | Aberrantly expressed in B-cell precursors |
Splicing | Canonical splicing with full-length DUX4 transcripts. | Initiates alternative splicing in target genes (e.g., ERGalt). |
Associated Diseases | FSHD, advanced-stage solid cancers | B-cell acute lymphoblastic leukaemia |
Immune Evasion | Downregulates chemokines and MHC class I in advanced-stage solid cancers. | Downregulates immune-related pathways, e.g., cytokine signalling |
