Eda-activated RelB recruits an SWI/SNF (BAF) chromatin-remodeling complex and initiates gene transcription in skin appendage formation

Autor: Elin Lehrmann, Weidong Wang, Zhong Wang, Jian Sima, Yongqing Zhang, Ramaiah Nagaraja, Zhijiang Yan, David Schlessinger, Yaohui Chen
Rok vydání: 2018
Předmět:
Zdroj: Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
0027-8424
DOI: 10.1073/pnas.1800930115
Popis: Significance Specific gene regulation in organ development remains poorly understood. Here, we report that skin-specific ectodysplasin A (Eda) signaling triggers the formation of a protein complex that includes a BAF complex, an NF-kB dimer of p50/RelB, and a specific “linker” protein, Tfg. We further find that Eda-activated RelB recruits BAF complex to specific gene loci for local chromatin remodeling of target genes. These findings may exemplify a more general model for specific gene regulation involving unique ligand–receptor complexes leading to selective activation of transcription factors, specific linkers, and tissue-specific chromatin-remodeling complex.
Ectodysplasin A (Eda) signaling activates NF-κB during skin appendage formation, but how Eda controls specific gene transcription remains unclear. Here, we find that Eda triggers the formation of an NF-κB–associated SWI/SNF (BAF) complex in which p50/RelB recruits a linker protein, Tfg, that interacts with BAF45d in the BAF complex. We further reveal that Tfg is initially induced by Eda-mediated RelB activation and then bridges RelB and BAF for subsequent gene regulation. The BAF component BAF250a is particularly up-regulated in skin appendages, and epidermal knockout of BAF250a impairs skin appendage development, resulting in phenotypes similar to those of Eda-deficient mouse models. Transcription profiling identifies several target genes regulated by Eda, RelB, and BAF. Notably, RelB and the BAF complex are indispensable for transcription of Eda target genes, and both BAF complex and Eda signaling are required to open chromatin of Eda targets. Our studies thus suggest that Eda initiates a signaling cascade and recruits a BAF complex to specific gene loci to facilitate transcription during organogenesis.
Databáze: OpenAIRE