The <scp>CREB</scp>‐binding protein affects the circadian regulation of behaviour

Maurer, Christian; Winter, Tobias; Chen, Siwei; Hung, Hsiu-Cheng; Weber, Frank

doi:10.1002/1873-3468.12336

Cited by 11 publications

(7 citation statements)

References 39 publications

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“…Similar to what we observed in mice, when CBP levels are decreased in circadian pacemaker neurons, the period is lengthened in Drosophila (95). Moreover, the regulation of CBP levels appears to be a critical factor in the maintenance of normal circadian function as overexpression of CBP induces behavioral arrhythmicity in Drosophila (93,96).…”

Section: Discussionsupporting

confidence: 83%

“…The role of CBP in the circadian clock appears highly conserved. In Drosophila, CBP has been shown important in circadian gene transcription regulating the CLOCK/CYCLE activation of transcription (93)(94)(95)(96). Similar to what we observed in mice, when CBP levels are decreased in circadian pacemaker neurons, the period is lengthened in Drosophila (95).…”

Section: Discussionsupporting

confidence: 83%

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The CBP KIX domain regulates long-term memory and circadian activity

Chatterjee

Angelakos

Bahl

et al. 2020

Preprint

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CREB-dependent transcription necessary for long-term memory is driven by interactions with CREB-binding protein (CBP), a multi-domain protein that binds numerous transcription factors. Identifying specific domain functions for multi-action proteins is essential to understand processes necessary for healthy living including cognitive function and a robust circadian clock. We investigated the function of the CBP KIX domain in hippocampal memory and gene expression using CBP KIX/KIX mice with mutations that prevent phospho-CREB (Ser133) binding. We found that CBP KIX/KIX mice were impaired in long-term, but not short-term spatial memory in the Morris water maze. Using an unbiased analysis of gene expression after training for hippocampus-dependent memory, we discovered dysregulation of CREB and CLOCK target genes and downregulation of circadian genes in CBP KIX/KIX mice.With our finding that the CBP KIX domain was important for transcription of circadian genes, we profiled circadian activity in CBP KIX/KIX mice. CBP KIX/KIX mice exhibited delayed activity peaks after light offset and longer free-running periods in constant dark, although phase resetting to light was comparable to wildtype. These studies provide insight into the significance of the CBP KIX domain by defining targets of CBP transcriptional co-activation in memory and the role of the CBP KIX domain in vivo on circadian rhythms.

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Section: Discussionsupporting

confidence: 83%

Section: Discussionsupporting

confidence: 83%

The CBP KIX domain regulates long-term memory and circadian activity

Chatterjee

Angelakos

Bahl

et al. 2020

Preprint

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“…Using an unbiased approach to study CA1 neuronal FMRP targets, we identified circadian genes as the most significant set of CA1 transcripts enriched in both CLIP-binding and showing changes in ribosome association in Fmr1 KO by CA1 TRAP (Figure 4B). Among our list of stringent CA1 targets are Npas2, a core component of the circadian clock, Ppargc1a, a key component of the circadian oscillator that integrates the mammalian clock and energy metabolism (Liu et al, 2007), Ncoa2, a coactivator of the key transcription BMAL1:CLOCK regulatory complex of the circadian clock (Stashi et al, 2014) and Crebbp, a coactivator of circadian transcription and a regulator of circadian behavior downstream of the circadian clock (Hung et al, 2007; Lim et al, 2007; Maurer et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

FMRP has a cell-type-specific role in CA1 pyramidal neurons to regulate autism-related transcripts and circadian memory

Sawicka

Hale

Park

et al. 2019

eLife

136

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Loss of the RNA binding protein FMRP causes Fragile X Syndrome (FXS), the most common cause of inherited intellectual disability, yet it is unknown how FMRP function varies across brain regions and cell types and how this contributes to disease pathophysiology. Here we use conditional tagging of FMRP and CLIP (FMRP cTag CLIP) to examine FMRP mRNA targets in hippocampal CA1 pyramidal neurons, a critical cell type for learning and memory relevant to FXS phenotypes. Integrating these data with analysis of ribosome-bound transcripts in these neurons revealed CA1-enriched binding of autism-relevant mRNAs, and CA1-specific regulation of transcripts encoding circadian proteins. This contrasted with different targets in cerebellar granule neurons, and was consistent with circadian defects in hippocampus-dependent memory in Fmr1 knockout mice. These findings demonstrate differential FMRP-dependent regulation of mRNAs across neuronal cell types that may contribute to phenotypes such as memory defects and sleep disturbance associated with FXS.

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“…The role of CBP in the circadian clock appears highly conserved. In Drosophila , CBP has been shown important in circadian gene transcription regulating the CLOCK/CYCLE activation of transcription [ 94 – 97 ]. Similar to what we observed in mice, when CBP levels are decreased in circadian pacemaker neurons, the period is lengthened in Drosophila [ 96 ].…”

Section: Discussionmentioning

confidence: 99%

“…Similar to what we observed in mice, when CBP levels are decreased in circadian pacemaker neurons, the period is lengthened in Drosophila [ 96 ]. Moreover, the regulation of CBP levels appears to be a critical factor in the maintenance of normal circadian function as overexpression of CBP induces behavioral arrhythmicity in Drosophila [ 94 , 97 ].…”

Section: Discussionmentioning

confidence: 99%

The CBP KIX domain regulates long-term memory and circadian activity

et al. 2020

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Background CREB-dependent transcription necessary for long-term memory is driven by interactions with CREB-binding protein (CBP), a multi-domain protein that binds numerous transcription factors potentially affecting expression of thousands of genes. Identifying specific domain functions for multi-domain proteins is essential to understand processes such as cognitive function and circadian clocks. We investigated the function of the CBP KIX domain in hippocampal memory and gene expression using CBPKIX/KIX mice with mutations that prevent phospho-CREB (Ser133) binding. Results We found that CBPKIX/KIX mice were impaired in long-term memory, but not learning acquisition or short-term memory for the Morris water maze. Using an unbiased analysis of gene expression in the dorsal hippocampus after training in the Morris water maze or contextual fear conditioning, we discovered dysregulation of CREB, CLOCK, and BMAL1 target genes and downregulation of circadian genes in CBPKIX/KIX mice. Given our finding that the CBP KIX domain was important for transcription of circadian genes, we profiled circadian activity and phase resetting in CBPKIX/KIX mice. CBPKIX/KIX mice exhibited delayed activity peaks after light offset and longer free-running periods in constant dark. Interestingly, CBPKIX/KIX mice displayed phase delays and advances in response to photic stimulation comparable to wildtype littermates. Thus, this work delineates site-specific regulation of the circadian clock by a multi-domain protein. Conclusions These studies provide insight into the significance of the CBP KIX domain by defining targets of CBP transcriptional co-activation in memory and the role of the CBP KIX domain in vivo on circadian rhythms. Graphical abstract

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The CREB‐binding protein affects the circadian regulation of behaviour

Cited by 11 publications

References 39 publications

The CBP KIX domain regulates long-term memory and circadian activity

The CBP KIX domain regulates long-term memory and circadian activity

FMRP has a cell-type-specific role in CA1 pyramidal neurons to regulate autism-related transcripts and circadian memory

The CBP KIX domain regulates long-term memory and circadian activity

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