Protocol for bulk and single-nuclei chromatin accessibility quantification in mouse liver tissue

Korenfeld, Noga; Toft, Nicolaj I.; Dam, Trine V.; Charni-Natan, Meital; Grøntved, Lars; Goldstein, Ido

doi:10.1016/j.xpro.2023.102462

Cited by 2 publications

(2 citation statements)

References 9 publications

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“…The multiplex sample pool (1.6 pM including PhiX 1%) was loaded on NextSeq 500/550 High Output v2 kit (75 cycles) cartridge, and loaded onto the NextSeq 500 System (Illumina), with 75 cycles and single-read sequencing conditions. ATAC-seq: ATAC-seq was performed as described in our published protocol 47 . Briefly, nuclei were isolated using a hypotonic buffer and Dounce homogenizer.…”

Section: Methodsmentioning

confidence: 99%

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Repeated fasting events sensitize enhancers, transcription factor activity and gene expression to support augmented ketogenesis

Korenfeld,

Charni-Natan,

Bruse

et al. 2024

Preprint

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Mammals withstand frequent and prolonged fasting periods due to hepatic production of ketone bodies. Because the fasting response is transcriptionally-regulated, we asked whether enhancer dynamics impose a transcriptional program during recurrent fasting and whether this generates effects distinct from a single fasting bout. We found that mice undergoing alternate-day fasting (ADF) respond profoundly differently to a following fasting bout compared to mice first experiencing fasting. Hundreds of genes enabling ketogenesis are sensitized (induced more strongly by fasting following ADF). Liver enhancers regulating these genes are also sensitized and harbor increased binding of PPAR alpha, the main ketogenic transcription factor. ADF leads to augmented ketogenesis compared to a single fasting bout in wild-type, but not hepatocyte-specific PPAR alpha-deficient mice. Thus, we found that past fasting events are remembered in hepatocytes, sensitizing their enhancers to the next fasting bout and augment ketogenesis. Our findings shed light on transcriptional regulation mediating adaptation to repeated signals.

show abstract

Section: Methodsmentioning

confidence: 99%

“…ATAC-seq was performed as described in our published protocol 47 . Briefly, nuclei were isolated using a hypotonic buffer and Dounce homogenizer.…”

Section: Methodsmentioning

confidence: 99%

Repeated fasting events sensitize enhancers, transcription factor activity and gene expression to support augmented ketogenesis

Korenfeld,

Charni-Natan,

Bruse

et al. 2024

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

Repeated fasting events sensitize enhancers, transcription factor activity and gene expression to support augmented ketogenesis

Korenfeld,

Charni-Natan,

Bruse

et al. 2024

Nucleic Acids Research

View full text Add to dashboard Cite

Mammals withstand frequent and prolonged 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 generates effects distinct from a single fasting bout. We found that mice undergoing alternate-day fasting (ADF) respond profoundly differently to a following fasting bout compared to mice first experiencing fasting. Hundreds of genes enabling ketogenesis are ‘sensitized’ (i.e. induced more strongly by fasting following ADF). Liver enhancers regulating these genes are also sensitized and harbor increased binding of PPARα, the main ketogenic transcription factor. ADF leads to augmented ketogenesis compared to a single fasting bout in wild-type, but not hepatocyte-specific PPARα-deficient mice. Thus, we found that past fasting events are ‘remembered’ in hepatocytes, sensitizing their enhancers to the next fasting bout and augment ketogenesis. Our findings shed light on transcriptional regulation mediating adaptation to repeated signals.

show abstract

Protocol for bulk and single-nuclei chromatin accessibility quantification in mouse liver tissue

Cited by 2 publications

References 9 publications

Repeated fasting events sensitize enhancers, transcription factor activity and gene expression to support augmented ketogenesis

Repeated fasting events sensitize enhancers, transcription factor activity and gene expression to support augmented ketogenesis

Repeated fasting events sensitize enhancers, transcription factor activity and gene expression to support augmented ketogenesis

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