XBP1 controls diverse cell type- and condition-specific transcriptional regulatory networks.

TitleXBP1 controls diverse cell type- and condition-specific transcriptional regulatory networks.
Publication TypeJournal Article
Year of Publication2007
AuthorsAcosta-Alvear D, Zhou Y, Blais A, Tsikitis M, Lents NH, Arias C, Lennon CJ, Kluger Y, Dynlacht BDavid
JournalMol Cell
Date Published2007 Jul 6
KeywordsAnimals, Base Sequence, Basic Helix-Loop-Helix Transcription Factors, Binding Sites, Chromatin Immunoprecipitation, Computational Biology, DNA-Binding Proteins, Endoplasmic Reticulum, Energy Metabolism, Gene Expression Regulation, Gene Regulatory Networks, Genome, Mice, Molecular Sequence Data, Muscle Development, Muscle, Skeletal, Muscular Diseases, Neurodegenerative Diseases, Nuclear Proteins, Protein Binding, Protein Folding, Rats, Reproducibility of Results, Substrate Specificity, Transcription Factors

Using genome-wide approaches, we have elucidated the regulatory circuitry governed by the XBP1 transcription factor, a key effector of the mammalian unfolded protein response (UPR), in skeletal muscle and secretory cells. We identified a core group of genes involved in constitutive maintenance of ER function in all cell types and tissue- and condition-specific targets. In addition, we identified a cadre of unexpected targets that link XBP1 to neurodegenerative and myodegenerative diseases, as well as to DNA damage and repair pathways. Remarkably, we found that XBP1 regulates functionally distinct targets through different sequence motifs. Further, we identified Mist1, a critical regulator of differentiation, as an important target of XBP1, providing an explanation for developmental defects associated with XBP1 loss of function. Our results provide a detailed picture of the regulatory roadmap governed by XBP1 in distinct cell types as well as insight into unexplored functions of XBP1.

Alternate JournalMol. Cell
PubMed ID17612490
Grant ListGM067132-03 / GM / NIGMS NIH HHS / United States