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Series GSE212776 Query DataSets for GSE212776
Status Public on Nov 18, 2024
Title Repeated fasting events sensitize chromatin and gene expression to support augmented ketogenesis
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Summary Mammals evolved to withstand frequent fasting periods due to hepatic production of glucose and ketone bodies. Because the fasting response is transcriptionally-regulated, we asked whether enhancer dynamics impose a transcriptional program during recurrent fasting and whether this produces effects distinct from a single fasting bout. We found that mice undergoing alternate-day fasting (ADF) respond to a following fasting bout profoundly differently from mice first experiencing fasting. Hundreds of genes enabling ketogenesis are ‘sensitized’, i.e. induced more strongly by fasting following ADF. Enhancers regulating these genes are also sensitized and harbor increased binding of the major ketogenic transcription factor. ADF mice show augmented ketogenesis and their sensitized enhancers are covalently marked with ketone body residues. Thus, we found that past fasting events are ‘remembered’ in hepatocytes, sensitizing their enhancers to the next fasting bout and augmenting ketogenesis. Our findings shed light on transcriptional regulation mediating adaptation to repeated environmental signals.
 
Overall design Mice were subjected to either a 4-week alternate day fasting (ADF) regimen or unrestricted feeding (URF). At the end of the experiment mice were divided to 3 groups: the first group was euthanized after a 24 h fasting period (ADF_f or URF_f). The second group fasted for 24 h followed by ad libitum refeeding for 24 h at the end of which they were euthanized (ADF_re or URF_re). The third group did not experience any type of fasting (unrestricted feeding). Each group has 3 replicates.
 
Contributor(s) Goldstein I, Korenfeld N, Charni-Natan M
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Submission date Sep 06, 2022
Last update date Nov 19, 2024
Contact name Ido Goldstein
Organization name The Hebrew University of Jerusalem
Department Institute of Biochemistry, Food Science and Nutrition
Street address POB 12
City Rehovot
ZIP/Postal code 7610001
Country Israel
 
Platforms (2)
GPL19057 Illumina NextSeq 500 (Mus musculus)
GPL21626 NextSeq 550 (Mus musculus)
Samples (34)
GSM6547569 rna, urf_f, 1
GSM6547570 rna, urf_f, 2
GSM6547571 rna, urf_f, 3
Relations
BioProject PRJNA877234

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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE212776_RAW.tar 7.7 Gb (http)(custom) TAR (of BEDGRAPH)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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