AI Article Synopsis
- JADE is a key part of the HBO1 acetyltransferase complex, which plays a significant role in regulating gene transcription and developmental processes.
- The PZP domain of JADE binds to histone H3 and DNA, facilitating the recruitment of the HBO1 complex to chromatin and influencing its enzymatic activity based on the methylation status of H3K4.
- JADE’s involvement is linked to leukemogenesis, enhancing the activity of specific fusion proteins, indicating its critical role in both normal and pathological cellular functions.
Article Abstract
JADE is a core subunit of the HBO1 acetyltransferase complex that regulates developmental and epigenetic programs and promotes gene transcription. Here we describe the mechanism by which JADE facilitates recruitment of the HBO1 complex to chromatin and mediates its enzymatic activity. Structural, genomic and complex assembly in vivo studies show that the PZP (PHD1-zinc-knuckle-PHD2) domain of JADE engages the nucleosome through binding to histone H3 and DNA and is necessary for the association with chromatin targets. Recognition of unmethylated H3K4 by PZP directs enzymatic activity of the complex toward histone H4 acetylation, whereas H3K4 hypermethylation alters histone substrate selectivity. We demonstrate that PZP contributes to leukemogenesis, augmenting transforming activity of the NUP98-JADE2 fusion. Our findings highlight biological consequences and the impact of the intact JADE subunit on genomic recruitment, enzymatic function and pathological activity of the HBO1 complex.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11320721 | PMC |
| http://dx.doi.org/10.1038/s41594-024-01245-2 | DOI Listing |
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