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Transcription Factors Form a Ternary Complex with NIPBL/MAU2 to Localize Cohesin at Enhancers

ABSTRACT: The cohesin complex is a key player in dynamic genome architecture adjustments. The loading of the cohesin complex on chromatin is believed to be achieved by the cohesin-loader Nipped-B homolog (NIPBL). Recently, we and others proposed that direct interactions with transcriptions factors (TFs) would lead to accurate positioning of NIPBL on the DNA. In this study, we identified remarkable protein-protein interaction motifs (PPIMs) in the NIPBL sequence. Mutations of those motifs dramatically alters: (i) the global NIPBL chromatin binding, (ii) the NIPBL-dependent transcriptional program and (iii) the NIPBL proteome network including TFs. While we found that the MAU2/NIPBL interaction was relying on those PPIMs, we further discovered that MAU2 was directly interacting with dozens of TFs. Concomitantly, we found that numerous TFs were also able to interact with NIPBL through PPIMs. Finally, using nuclear receptors as models and then focusing on the Glucocorticoid Receptor (GR), we mechanistically dissect a trimeric complex formed by GR, NIPBL and MAU2 and investigate the importance of those interactions for GR transcriptional program.

ORGANISM(S): Mus musculus

PROVIDER: GSE282583 | GEO | 2025/01/31

REPOSITORIES: GEO

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