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| Status |
Public on Sep 19, 2022 |
| Title |
A molecular pathway for transcriptional regulation of daily sleep need in mice |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Different mammalian species vary greatly in their daily sleep quota, ranging from 2-4 hours in giraffes to 20-22 hours in koalas and bats. In humans, the sleep quantity and quality of individuals are governed by genetic factors and exhibit age-dependent variations. However, the molecular pathways and effector mechanisms that regulate daily sleep need in mammals remain unknown. Here, using an adult brain chimeric (ABC)-expression/knockout (KO) system for somatic genetics analysis of sleep in adult mice, we report that gain-of-function of histone deacetylases HDAC4/5 significantly reduces, whereas loss-of-function of HDAC4/5 increases daily non-rapid eye movement sleep (NREMS) amount and delta power–two key indicators of sleep need. Similarly, ABC-expression of cAMP-response element binding protein (CREB) or A-CREB, an inhibitor of transcriptional activity of CREB, decreases or increases NREMS amount and delta power, respectively. A combination of genetic and transcriptomic analysis reveals that HDAC4 functions in tandem with CREB in both transcriptional and sleep regulation. Consistent with their functions downstream of LKB1-SIK3 kinase cascade, ABC-expression of HDAC4/5CA or CREB rescues hypersomnia of Sik3E13∆/+ mice, whereas ABC-expression of SIK3/SLP-ST221E or HDAC(4+5)VP16 rescues insomnia of ABC-Lkb1KO mice. Taken together, these results identify LKB1-SIK3-HDAC4/5-CREB as the first major molecular pathway for transcriptional regulation of daily sleep need in mammals.
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| Overall design |
1. CREB bound genomic DNA. 2. HDAC4CA bound genomic DNA. 3.IgG ChIP as negative control.
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| Contributor(s) |
Zhou R, Ju D, Liao M, Liu Q |
| Citation(s) |
36477534 |
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| Submission date |
Aug 26, 2021 |
| Last update date |
Dec 16, 2022 |
| Contact name |
dapeng ju |
| E-mail(s) |
judapeng19851008@gmail.com
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| Organization name |
Department of Anesthesiology The Second Affiliated Hospital,,Chongqing Medical University ,
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| Street address |
1 Yixueyuan Road, Yuzhong District
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| City |
Chongqing |
| ZIP/Postal code |
400060 |
| Country |
China |
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| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA757954 |
| SRA |
SRP334372 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE182805_RAW.tar |
866.3 Mb |
(http)(custom) |
TAR (of BW) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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