AI Article Synopsis
- Histone reader modules, like Spindlin1, are critical for epigenetic regulation by recognizing specific methylation patterns on histones.
- Spindlin1 not only reads histone H3K4me3 but also targets a complex "K4me3-K9me3/2" bivalent methylation pattern with a strong binding affinity, implying a significant role in gene transcription processes.
- This study indicates that Spindlin1 interacts with both H3K4me3 and H3K9me3, primarily affecting gene expression in regions marked by H3K4me3, thus influencing the balance between gene activation and silencing.
Article Abstract
Histone recognition by "reader" modules serves as a fundamental mechanism in epigenetic regulation. Previous studies have shown that Spindlin1 is a reader of histone H3K4me3 as well as "K4me3-R8me2a" and promotes transcription of rDNA or Wnt/TCF4 target genes. Here we show that Spindlin1 also acts as a potent reader of histone H3 "K4me3-K9me3/2" bivalent methylation pattern. Calorimetric titration revealed a binding affinity of 16 nm between Spindlin1 and H3 "K4me3-K9me3" peptide, which is one to three orders of magnitude stronger than most other histone readout events at peptide level. Structural studies revealed concurrent recognition of H3K4me3 and H3K9me3/2 by aromatic pockets 2 and 1 of Spindlin1, respectively. Epigenomic profiling studies showed that Spindlin1 colocalizes with both H3K4me3 and H3K9me3 peaks in a subset of genes enriched in biological processes of transcription and its regulation. Moreover, the distribution of Spindlin1 peaks is primarily associated with H3K4me3 but not H3K9me3, which suggests that Spindlin1 is a downstream effector of H3K4me3 generated in heterochromatic regions. Collectively, our work calls attention to an intriguing function of Spindlin1 as a potent H3 "K4me3-K9me3/2" bivalent mark reader, thereby balancing gene expression and silencing in H3K9me3/2-enriched regions.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7864079 | PMC |
| http://dx.doi.org/10.1074/jbc.RA120.013649 | DOI Listing |
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