Abstract
The cyclic AMP response element binding protein (CREB) is a primary hub of activity-driven genetic programs in neurons controlling plasticity, neurogenesis and survival. By contrast, the gene networks coordinated by CREB in astrocytes are unknown despite the fact that the astrocytic CREB is also activity-driven and neuroprotective. Herein we identified the transcriptional programs regulated by CREB in astrocytes as compared to neurons using, as study materials, transcriptome databases of astrocyte exposed to well-known activators of CREB-dependent transcription as well as publicly available transcriptomes of neuronal cultures. Functional CREB signatures were extracted from the transcriptomes using Gene Ontology, adult-brain gene lists generated by Translating Ribosome Affinity Purification (TRAP) and CREB-target gene repositories. We found minimal overlap between CREB signatures in astrocytes and neurons. In astrocytes, the top triad of functions regulated by CREB consists of ‘Gene expression’, ‘Mitochondria’, and ‘Signalling’, while in neurons it is ‘Neurotransmission’, ‘Signalling’ and ‘Gene expression’, the latter two being represented by different genes from those in astrocytes. The newly generated databases will provide a tool to explore novel means whereby CREB impinges on brain functions requiring adaptive, long-lasting changes by coordinating transcriptional cascades in astrocytes.
Highlights
IntroductionThe newly generated databases will provide a tool to explore novel means whereby cyclic AMP response element binding protein (CREB) impinges on brain functions requiring adaptive, long-lasting changes by coordinating transcriptional cascades in astrocytes
1) cyclic AMP response element binding protein (CREB)-dependent transcription was activated in primary cortical rat astrocyte cultures with 10 μM NE, 1 μM FSK or VP16-CREB
We examined whether DEG-Q1TRAP lists were enriched in transcriptomes from adult brains with targeted expression of VP16-CREB in astrocytes[9]
Summary
The newly generated databases will provide a tool to explore novel means whereby CREB impinges on brain functions requiring adaptive, long-lasting changes by coordinating transcriptional cascades in astrocytes. Since its discovery in the late 1980s, the cyclic AMP-response element-binding protein (CREB) is arguably the most widely studied transcription factor, its two best documented functions being the coordination of liver metabolism during cycles of feeding and fasting[1], and the regulation of neuronal plasticity—defined as long-term adaptive changes—in several scenarios: development, memory acquisition and consolidation, addiction, circadian rhythms and natural regeneration after injury[2,3,4,5]. CREB-dependent transcription is activated in astrocytes by noradrenaline (NE), ATP, forskolin (FSK), tamoxifen and cinnamon[6,7,8]. The targeted expression of a constitutively active CREB construct (VP16-CREB) in astrocytes is neuroprotective in focal acute brain injury[9]
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