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Vock, I. W.

Publications and source records attributed to Vock, I. W..

2 recordsLinked to original sources

Differential kinetic analysis using nucleotide recoding RNA-seq and bakR

Conventional RNA sequencing (RNA-seq) provides limited information about the kinetic mechanisms underlying changes in RNA levels. Nucleotide recoding RNA-seq methods (NR-seq; e.g., TimeLapse-seq, SLAM-seq, etc.) are widely used approaches to identify changes in RNA synthesis and degradation kinetics, yet no software exists to rigorously compare the parameters of RNA kinetics between experimental conditions. We developed bakR to address this need. bakR relies on Bayesian hierarchical modeling of NR-seq data to increase statistical power by sharing information across transcripts. Using simulated and real data, we validate bakR and demonstrate how it provides new insights into the kinetics of RNA metabolism.

bioinformatics↗

A Dual-Site Inhibitor of CBP/p300 KIX is a Selective and Effective Modulator of Myb

The protein-protein interaction between the KIX motif of the transcriptional coactivator CBP/p300 and the transcriptional activator Myb is a high value target due to its established role in certain acute myeloid leukemias (AML) and potential contributions to other cancers. However, the CBP/p300 KIX domain has multiple binding sites, several structural homologues, many binding partners, and substantial conformational plasticity, making it challenging to specifically target using small molecule inhibitors. Here, we report a picomolar dual-site inhibitor (MybLL-tide) of the Myb-CBP/p300 KIX interaction. MybLL-tide has higher affinity for CBP/p300 KIX than any previously reported compounds while also possessing 16,000-fold selectivity for the CBP/p300 KIX domain over other coactivator domains. MybLL-tide blocks the association of CBP and p300 with Myb in the context of the proteome leading to inhibition of key Myb*KIX-dependent genes in AML cells. These results show that MybLL-tide is an effective, modifiable tool to selectively target the KIX domain and assess transcriptional effects in AML cells and potentially other cancers featuring aberrant Myb behavior. Additionally, the dual-site design has applicability to the other challenging coactivators that bear multiple binding surfaces

biochemistry↗