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

Aging Cell
Holly WhittonIrina M Bochkis

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 an...Continue Reading

References

Feb 2, 2000·Nature Genetics·S ShackletonR C Trembath
Aug 16, 2005·Cell Metabolism·Liping ZhangKlaus H Kaestner
Aug 16, 2006·Cellular and Molecular Life Sciences : CMLS·J R Friedman, K H Kaestner
Apr 30, 2008·Human Molecular Genetics·Guillermo MariñoCarlos López-Otín
Jun 27, 2008·Proceedings of the National Academy of Sciences of the United States of America·Louisa M VilleneuveRama Natarajan
Jan 6, 2009·Nature Biotechnology·Joel RozowskyMark B Gerstein
Apr 11, 2009·Trends in Endocrinology and Metabolism : TEM·Nikolai A Timchenko
May 7, 2009·Physiological Genomics·Irina M BochkisKlaus H Kaestner
May 20, 2009·Bioinformatics·Heng Li, Richard Durbin
Jul 18, 2009·Genes & Development·Alejandro Vaquero, Danny Reinberg
May 4, 2010·Nature Biotechnology·Cory Y McLeanGill Bejerano
Aug 12, 2010·Aging Cell·Jingling JinNikolai A Timchenko
Jan 12, 2011·Nature Biotechnology·James T RobinsonJill P Mesirov
May 31, 2011·Nature Structural & Molecular Biology·Zhaoyu LiKlaus H Kaestner
Nov 8, 2011·Genes & Development·Kenneth S Zaret, Jason S Carroll
Feb 19, 2015·PLoS Genetics·Tian YuanAndrew E Teschendorff
May 5, 2016·Nucleic Acids Research·Maxim V KuleshovAvi Ma'ayan
Aug 16, 2016·Cell·Carlos López-OtínGuido Kroemer
Feb 2, 2017·The Journal of Clinical Investigation·Suzanne Hood, Shimon Amir
Jun 14, 2017·Nature Communications·Mikolaj OgrodnikDiana Jurk
Sep 16, 2017·Cellular and Molecular Gastroenterology and Hepatology·Raymond KwanM Bishr Omary

❮ Previous
Next ❯

Citations

May 7, 2020·Nature Communications·Weiqi ZhangJing Qu
Aug 25, 2020·Science Advances·Nicolás G SimonetAlejandro Vaquero
Sep 22, 2018·Histochemistry and Cell Biology·Carmen AdriaensTom Misteli
Sep 5, 2020·Annual Review of Genetics·Kenneth S Zaret
Apr 24, 2020·Biochimica Et Biophysica Acta. Reviews on Cancer·Bing GaoJianping Guo

❮ Previous
Next ❯

Datasets Mentioned

BETA
GSE58006
GSE60393
GSE78177

Methods Mentioned

BETA
immunoprecipitation
DamID
ChIP
Ch
PCR

Software Mentioned

Galaxy
Ingenuity Pathway Analysis ( IPA )
PeakSeq
ImageJ
Integrative Genome Viewer ( IGV
PscanChiP
HOMER
Epic peak caller
GREAT
BWA

Related Concepts

Related Feeds

Cell Aging (Keystone)

This feed focuses on cellular aging with emphasis on the mitochondria, autophagy, and metabolic processes associated with aging and longevity. Here is the latest research on cell aging.