C/EBPβ and C/EBPδ transcription factors: Basic biology and roles in the CNS

CCAAT/enhancer binding protein (C/EBP) beta and C/EBP delta are transcription factors of the basic-leucine zipper class which share phylogenetic, structural and functional features. In this review we first describe in depth their basic molecular biology which includes fascinating aspects such as the regulated use of alternative initiation codons in the C/EBP beta mRNA. The physical interactions with multiple transcription factors which greatly opens the number of potentially regulated genes or the presence of at least five different types of post-translational modifications are also remarkable molecular mechanisms that modulate C/EBP beta and C/EBP delta function. In the second part, we review the present knowledge on the localization, expression changes and physiological roles of C/EBP beta and C/EBP delta in neurons, astrocytes and microglia. We conclude that C/EBP beta and C/EBP delta share two unique features related to their role in the CNS: whereas in neurons they participate in memory formation and synaptic plasticity, in glial cells they regulate the pro-inflammatory program. Because of their role in neuroinflammation, C/EBP beta and C/EBP delta in microglia are potential targets for treatment of neurodegenerative disorders. Any strategy to reduce C/EBP beta and C/EBP delta activity in neuroinflammation needs to take into account its potential side-effects in neurons. Therefore, cell-specific treatments will be required for the successful application of this strategy. (C) 2015 Elsevier Ltd. All rights reserved.