![Author ORCID: We display the ORCID iD icon alongside authors names on our website to acknowledge that the ORCiD has been authenticated when entered by the user. To view the users ORCiD record click the icon. [opens in a new tab]](https://chemrxiv.org/engage/assets/public/chemrxiv/images/logos/orcid.png)
Abstract
Lysine and arginine methylation are amongst the most frequent modifications on unstructured histone tails and in
combination with other modifications provide the basis for a combinatorial 'chromatin or histone code'. Recognition of modified
histone residues is accomplished in a specific manner by 'reader' domains that recognize chromatin modifications, allowing for
association with specific effector complexes that mediate chromatin functions. The methyl-lysine and methyl-arginine reader domain
protein SPINDLIN1 (SPIN1) belongs to a family of 5 human genes, and has been identified as a putative oncogene and transcriptional
co-activator. It contains three Tudor domains that are able to mediate chromatin binding. Here we report on the discovery
of a potent and selective bidentate Tudor domain inhibitor, which simultaneously engages Tudor domains 1 and 2 and effectively
competes with chromatin binding in cells. Inhibitor, chemoproteomic and knockdown studies in squamous cell carcinoma indicate
complex SPIN-mediated chromatin interactions leading to transcriptional changes in cellular differentiation processes.
Supplementary materials
Title
ONLINE Materials and Methods Fagan et al
Description
Actions
Title
SI Data 1 compounds Fagan et al
Description
Actions
Title
SI DATA 2 - RNAseq Pathway analysis
Description
Actions
Title
Supplementary Information Fagan et al JACS
Description
Actions
Title
Supplementary Notes Fagan et al
Description
Actions
