MYRF Is a Membrane-Associated Transcription Factor That Autoproteolytically Cleaves to Directly Activate Myelin Genes

• DOI: 10.1371/journal.pbio.1001625
• Publication Date: 2013-08-13T20:44:52Z
• Authors: Helena Bujalka; Matthias Koenning; Stacey Jackson; Victoria M. Perreau; Bernard Pope; Curtis M. Hay; Stanlislaw Mitew; Andrew F. Hill; Q. Richard Lu; Michael Wegner; Rajini Srinivasan; John Svaren; Melanie Willingham; Ben A. Barres; Ben Emery
• Keywords: 570; Chromatin Immunoprecipitation; Naturwissenschaftliche Fakultät -ohne weitere Spezifikation-; QH301-705.5; 610; -; OPCs; Cell Line; Mice; 03 medical and health sciences; vertebrate; ddc:570; Animals; Humans; Biology (General); Cells, Cultured; Myelin Sheath; 0303 health sciences; oligodendrocyte progenitor cells; Membrane Proteins; central nervous system; Oligodendroglia; Chancellery; Gene Expression Regulation; 3209 Neurosciences; Mutagenesis, Site-Directed; CNS; protein; Research Article; Transcription Factors

The myelination of axons is a crucial step during vertebrate central nervous system (CNS) development, allowing for rapid and energy efficient saltatory conduction nerve impulses. Accordingly, the differentiation oligodendrocytes, myelinating cells CNS, their expression myelin genes are under tight transcriptional control. We previously identified putative transcription factor, Myelin Regulatory Factor (Myrf), as being vital CNS myelination. Myrf required generation development also its maintenance in adult. It has been controversial, however, whether directly regulates transcription, with reports transmembrane domain lack nuclear localization. Here we show that membrane-associated factor undergoes an activating proteolytic cleavage to separate domain-containing C-terminal region from nuclear-targeted N-terminal region. Unexpectedly, this event occurs via protein related autoproteolytic intramolecular chaperone bacteriophage tail spike proteins, first time found play role eukaryotic proteins. Using ChIP-Seq product binds enhancer regions oligodendrocyte-specific genes. This binding defined DNA-binding consensus sequence strongly promotes target These findings identify novel example provide direct molecular mechanism regulation oligodendrocyte