Genomics

Dataset Information

2

Changes at the nuclear lamina alter binding of pioneer factor Foxa2 in aged liver.


ABSTRACT: Increasing evidence suggests that regulation of heterochromatin at the nuclear envelope underlies metabolic disease susceptibility and age-dependent metabolic changes, but the mechanism is unknown. Here we profile lamina-associated domains (LADs) using lamin B1 ChIP-Seq in young and old hepatocytes and find that, although lamin B1 resides at a large fraction of domains at both ages, a third of lamin B1-associated regions are bound exclusively at each age in vivo. Regions occupied by lamin B1 solely in young livers are enriched for the forkhead motif, bound by Foxa pioneer factors. We also show that Foxa2 binds more sites in Zmpste24 mutant mice, a progeroid laminopathy model, similar to increased Foxa2 occupancy in old livers. Aged and Zmpste24-deficient livers share several features, including nuclear lamina abnormalities, increased Foxa2 binding, de-repression of PPAR and LXR-dependent gene expression, and fatty liver. In old livers, additional Foxa2 binding is correlated to loss of lamin B1 and heterochromatin (H3K9me3 occupancy) at these loci. Our observations suggest that changes at the nuclear lamina are linked to altered Foxa2 binding, enabling opening of chromatin and de-repression of genes encoding lipid synthesis and storage targets that contribute to etiology of hepatic steatosis. Overall design: Genome-wide location analysis (ChIP-Seq) of lamin B1, H3K9me3, and H3K9me2 from young (3 months) and old (21 months) mouse livers and Foxa2 in wildtype and Zmpste24 KO 12-week mouse livers .

INSTRUMENT(S): Illumina HiSeq 2500 (Mus musculus)

ORGANISM(S): Mus Musculus

SUBMITTER: Irina Bochkis  

PROVIDER: GSE78177 | GEO | 2018-01-19

REPOSITORIES: GEO

Dataset's files

Source:
Action DRS
GSE78177_Foxa2_WT.bed.gz Bed
GSE78177_Foxa2_Zmpste24KO.bed.gz Bed
GSE78177_Old_H3K9me3.bed.gz Bed
GSE78177_Old_LaminB.bed.gz Bed
GSE78177_Young_H3K9me3.bed.gz Bed
Items per page:
1 - 5 of 6
altmetric image

Publications

Changes at the nuclear lamina alter binding of pioneer factor Foxa2 in aged liver.

Whitton Holly H   Singh Larry N LN   Patrick Marissa A MA   Price Andrew J AJ   Osorio Fernando G FG   López-Otín Carlos C   Bochkis Irina M IM  

Aging cell 20180227 3


Increasing evidence suggests that regulation of heterochromatin at the nuclear envelope underlies metabolic disease susceptibility and age-dependent metabolic changes, but the mechanism is unknown. Here, we profile lamina-associated domains (LADs) using lamin B1 ChIP-Seq in young and old hepatocytes and find that, although lamin B1 resides at a large fraction of domains at both ages, a third of lamin B1-associated regions are bound exclusively at each age in vivo. Regions occupied by lamin B1 so  ...[more]

Similar Datasets

| S-EPMC5946061 | BioStudies
| S-EPMC2064018 | BioStudies
| E-GEOD-60393 | BioStudies
| E-GEOD-49341 | BioStudies
| S-EPMC3666708 | BioStudies
2019-01-01 | S-EPMC6410836 | BioStudies
| S-EPMC6426468 | BioStudies
| S-EPMC8761005 | BioStudies
| E-GEOD-57809 | BioStudies
| S-EPMC4658601 | BioStudies