Survivin prevents the polycomb repressor complex 2 from methylating histone 3 lysine 27

Survivin in Synergy With Baf/Swi Complex Binds Bivalent Chromatin Regions and Activates Dna Damage Response in Cd4+ T Cells

“…In support of this, we observed a significant change of histone H3 marks after survivin inhibition and molecular interactions between survivin and the base of the BAF/SWI complex including subunits SMARCC1, SMARCB1, SMARCD1, and SMARCE1 (He et al, 2020), which illustrated how BAF/SWI complex was mobilized to chromatin. This model finds validation in a recent functional study which deduced the role of epigenetic modifications for affinity of BAF complex binding to chromatin (Mashtalir et al, 2021), and in our recent study which showed that survivin inhibited the PRC2 repressive complex which obstructed transcription (Jensen et al, 2023). Thus, the proposed interaction mode of survivin with the BAF/SWI complex combined with its inhibitory action on the PRC2 complex potentially permits gene transcription.…”

“…To investigate in detail the interaction between survivin and the BAF complex, we applied the compositional analysis of proteins comprising the conventional (c)BAF and polybromo(P)BAF complexes aiming to predict their interaction with survivin. For this purpose, we utilized the peptide model based on the functional group composition of each protein of the complex (Jensen et al, 2023; Anindya et al, 2024). We identified that SMARCD1, SMARCA2, SMARCA4, SMARCC1, and BRD7 exhibit comparable ratios between the predicted binding peptides to the total number of generated peptides (R bind ) values in the range of 0.39-0.43.…”

“…Conversely, ARID1A and ARID2 exhibit limited regions with R bind values of 0.24 and 0.19, respectively ( Supplementary Table T5 ), compared to the median R bind of the proteome. Our previous observations indicate that only specific domains of the core subunit of the PRC2 complex JARID2 contain a survivin binding region, despite large regions of JARID2 not binding survivin (Jensen et al, 2023). Therefore, mapping to sequence or 3D space becomes essential to identify clusters of polypeptide regions with suitable composition.…”

“…The peptides from the survivin binding custom designed microarray (n>5250, PEPperCHIP, Heidelberg, Germany) comprised a scikit-learn python library to implement the machine learning process, in which the peptides were divided into equally large training and test sets (Jensen et al, 2023). Based on the functional composition of the protein, defined by the presence of atomic groups (C, CH, CH 2 , CH 3 , hydroxyl, phenyl, carboxyl, amide, sulfhydryl, etc.)…”

“…Interaction of survivin with threonine 3 of histone H3 (Yamagishi et al, 2010; Niedzialkowska et al, 2012), together with our recent findings that survivin interacts with the catalytic subunit of the PRC2 repressive complex and inhibits trimethylation of histone H3K27 (Jensen et al, 2023), prompted us to investigate if survivin bound to the BvCR in CD4 + cells and if this binding effected CD4 + cell function. To examine this, we performed parallel chromatin sequencing in primary human CD4 + cells to annotate survivin to the BvCR and to explore the TF landscape of those BvCR to identify chromatin modifying complexes.…”