cAMP Response Element-Binding Protein Is a Primary Hub of Activity-Driven Neuronal Gene Expression

Abstract

Long-lasting forms of neuronal plasticity require de novo gene expression, but relatively little is known about the events that occur genome-wide in response to activity in a neuronal network. Here, we unveil the gene expression programs initiated in mouse hippocampal neurons in response to different stimuli and explore the contribution of four prominent plasticity-related transcription factors (CREB, SRF, EGR1, and FOS) to these programs. Our study provides a comprehensive view of the intricate genetic networks and interactions elicited by neuronal stimulation identifying hundreds of novel downstream targets, including novel stimulus-associated miRNAs and candidate genes that may be differentially regulated at the exon/promoter level. Our analyses indicate that these four transcription factors impinge on similar biological processes through primarily non-overlapping gene-expression programs. Meta-analysis of the datasets generated in our study and comparison with publicly available transcriptomics data revealed the individual and collective contribution of these transcription factors to different activity-driven genetic programs. In addition, both gain-and loss-of-function experiments support a pivotal role for CREB in membrane-to-nucleus signal transduction in neurons. Our data provide a novel resource for researchers wanting to explore the genetic pathways associated with activity-regulated neuronal functions.

Rit-mediated Stress Resistance Involves a p38-Mitogen- and Stress-activated Protein Kinase 1 (MSK1)-dependent cAMP Response Element-binding Protein (CREB) Activation Cascade

“…CREB and CREB-dependent gene expression has been implicated in promoting survival in a variety of tissues in response to protective stimuli, and CREB synthesis and phosphorylation promotes the expression of a large and diverse number of genes (6,8,9,11). Within the central nervous system (CNS), CREB is essential for normal neuronal development and for neuroprotection against a range of pathophysiological stimuli (7,8,37).…”

Parasites: evolution’s neurobiologists

“…see Cooper et al, 2003). For example, many neural functions are controlled by transcription factors (Benito et al, 2011). Because of the overlapping effects between different transcription factors, even if one is inhibited, other transcription factors can compensate to maintain normal neuronal function (Benito et al, 2011).…”

“…For example, many neural functions are controlled by transcription factors (Benito et al, 2011). Because of the overlapping effects between different transcription factors, even if one is inhibited, other transcription factors can compensate to maintain normal neuronal function (Benito et al, 2011). Such redundancy makes it difficult to induce specific behavioural changes, and may explain why parasites need multiple mechanisms.…”

cAMP-responsive Element-binding Protein (CREB) and cAMP Co-regulate Activator Protein 1 (AP1)-dependent Regeneration-associated Gene Expression and Neurite Growth

“…We next addressed the sufficiency and necessity of AP1 activity in driving Arg1 transcription by directly modulating AP1 activity using lentiviruses to express dominant-negative (AFos; referred to as Fos-DN) or constitutive-active (FosVP16; referred to as Fos-CA) variants of the Fos AP1 subunit (29,30). The expression of Fos-DN blocked Bt 2 cAMP-induced expression of an AP1 response element-driven luciferase reporter, whereas Fos-CA increased basal and Bt 2 cAMP-induced reporter activity (Fig.…”