Genomics

Dataset Information

0

A molecular pathway for transcriptional regulation of daily sleep need in mice


ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE182805 | GEO | 2022/09/19

REPOSITORIES: GEO

Dataset's files

Source:
Action DRS
Other
Items per page:
1 - 1 of 1

Similar Datasets

2022-09-18 | GSE182907 | GEO
| PRJNA757954 | ENA
2019-07-26 | GSE128871 | GEO
2016-03-21 | GSE75995 | GEO
2018-02-14 | GSE85335 | GEO
2019-07-03 | GSE133698 | GEO
2022-06-06 | GSE202304 | GEO
2016-09-07 | E-GEOD-78215 | biostudies-arrayexpress
2024-06-22 | PXD045652 | Pride
2016-09-07 | GSE78215 | GEO