AI Article Synopsis

  • Research indicates that the regulation of heterochromatin at the nuclear envelope may influence susceptibility to metabolic diseases and age-related metabolic changes, but the exact mechanisms remain unclear.
  • A study on lamin B1 in young and old liver cells reveals that while lamin B1 is present in many of the same regions at both ages, about one-third of those regions are uniquely associated with either young or old liver cells.
  • The findings suggest that age-related changes at the nuclear lamina may affect Foxa2 binding and gene expression related to lipid synthesis, which could play a role in the development of fatty liver in aging and certain genetic conditions.

Article 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.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5946061PMC
http://dx.doi.org/10.1111/acel.12742DOI Listing

Publication Analysis

Top Keywords

nuclear lamina
12
foxa2 binding
12
changes nuclear
8
increased foxa2
8
foxa2
6
lamin
5
lamina alter
4
binding
4
alter binding
4
binding pioneer
4

Similar Publications

Cellular activity is spatially organized across different organelles. While several structures are well-characterized, many organelles have unknown roles. Profiling biomolecular composition is key to understanding function but is difficult to achieve in the context of small, dynamic structures.

View Article and Find Full Text PDF

PRR14 mediates mechanotransduction and regulates myofiber identity via MEF2C in skeletal muscle.

Metabolism

December 2024

Hunan Key Laboratory of Tumor Models and Individualized Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China; Department of Orthopaedics, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China; Hunan Engineering Research Center of Artificial Intelligence Based Medical Equipment, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, China. Electronic address:

Skeletal muscle is a crucial tissue for physical activity and energy metabolism. Muscle atrophy, characterized by the loss of muscle mass and strength, contributes to adverse outcomes among individuals. This study elucidated the involvement of the nuclear lamina component PRR14 in transmitting mechanical signals and mediating the impact of exercise on skeletal muscle.

View Article and Find Full Text PDF

The nuclear lamina (NL) lines the nuclear envelope (NE) to maintain nuclear structure in metazoan cells. The major NL components, the nuclear lamins contribute to the protection against NE rupture induced by mechanical stress. Lamin A (LA) and a short form of the splicing variant lamin C (LC) are diffused from the nucleoplasm to sites of NE rupture in immortalized mouse embryonic fibroblasts (MEFs).

View Article and Find Full Text PDF

Understanding the level of genome organization that governs gene regulation remains a challenge despite advancements in chromatin profiling techniques. Cell type specific chromatin architectures may be obscured by averaging heterogeneous cell populations. Here we took a reductionist perspective, starting with the relocation of the gene to the nuclear lamina in neuroblasts.

View Article and Find Full Text PDF

Hutchinson-Gilford Progeria Syndrome (HGPS) is a rare genetic condition characterized by features of accelerated aging, and individuals with HGPS seldom live beyond their mid-teens. The syndrome is commonly caused by a point mutation in the LMNA gene which codes for lamin A and its splice variant lamin C, components of the nuclear lamina. The mutation causing HGPS leads to production of a truncated, farnesylated form of lamin A referred to as "progerin.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!

A PHP Error was encountered

Severity: Notice

Message: fwrite(): Write of 34 bytes failed with errno=28 No space left on device

Filename: drivers/Session_files_driver.php

Line Number: 272

Backtrace:

A PHP Error was encountered

Severity: Warning

Message: session_write_close(): Failed to write session data using user defined save handler. (session.save_path: /var/lib/php/sessions)

Filename: Unknown

Line Number: 0

Backtrace: