CREB Regulates Distinct Adaptive Transcriptional Programs in Astrocytes and Neurons
Sci Rep. 2017-07-25; 7(1):
DOI: 10.1038/s41598-017-06231-x
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1. Sci Rep. 2017 Jul 25;7(1):6390. doi: 10.1038/s41598-017-06231-x.
CREB Regulates Distinct Adaptive Transcriptional Programs in Astrocytes and
Neurons.
Pardo L(1), Valor LM(2), Eraso-Pichot A(3), Barco A(4), Golbano A(3), Hardingham
GE(5)(6), Masgrau R(3), Galea E(7)(8).
Author information:
(1)Institut de Neurociències and Unitat de Bioquímica, Facultat de Medicina,
Universitat Autònoma de Barcelona, Bellaterra, 08193, Barcelona, Spain.
.
(2)Unidad de Investigación, Hospital Universitario Puerta del Mar, Av. Ana de
Viya 21, 11009, Cádiz, Spain.
(3)Institut de Neurociències and Unitat de Bioquímica, Facultat de Medicina,
Universitat Autònoma de Barcelona, Bellaterra, 08193, Barcelona, Spain.
(4)Instituto de Neurociencias, Universidad Miguel Hernández/Consejo Superior de
Investigaciones Científicas, Sant Joan d’Alacant, 03550, Alicante, Spain.
(5)UK Dementia Research Institute at The University of Edinburgh, Edinburgh
Medical School, 47 Little France Crescent, Edinburgh, EH16 4TJ, UK.
(6)Deanery of Biomedical Sciences, Edinburgh Medical School, University of
Edinburgh, Edinburgh, EH8 9XD, UK.
(7)Institut de Neurociències and Unitat de Bioquímica, Facultat de Medicina,
Universitat Autònoma de Barcelona, Bellaterra, 08193, Barcelona, Spain.
.
(8)ICREA, Pg. Lluís Companys 23, 08010, Barcelona, Spain. .
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.
DOI: 10.1038/s41598-017-06231-x
PMCID: PMC5526874
PMID: 28743894 [Indexed for MEDLINE]