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Epigenetics is the study of inherited changes in a cell's phenotype without changing the DNA sequences. It provides a form of memory for the differential gene expression pattern to maintain cell lineage, position-effect variegation, dosage compensation, and maintenance of chromatin structures such as telomeres and centromeres. For example, the structure and location of the centromere on chromosomes are epigenetically inherited. Its functionality is not dictated or ensured by the underlying...
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  2. Research Domains
  3. Biological Sciences
  4. Genetics
  5. Epigenetics (incl. Genome Methylation And Epigenomics)
  6. The Activity Of Early-life Gene Regulatory Elements Is Hijacked In Aging Through Pervasive Ap-1-linked Chromatin Opening

The activity of early-life gene regulatory elements is hijacked in aging through pervasive AP-1-linked chromatin opening

Ralph Patrick1, Marina Naval-Sanchez1, Nikita Deshpande2

  • 1Institute for Molecular Bioscience, The University of Queensland, St. Lucia, Brisbane, QLD 4072, Australia.

Cell Metabolism
|July 3, 2024

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CRISPR-Mediated Reorganization of Chromatin Loop Structure
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View abstract on PubMed

Summary
This summary is machine-generated.

Aging and development share a common transcription factor binding site (TFBS) signature. Early-life elements lose accessibility, while others gain it, driven by activator protein 1 (AP-1) and chromatin changes, impacting gene expression.

Keywords:
AP-1CTCFagingcell identity

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CRISPR-Mediated Reorganization of Chromatin Loop Structure
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Area of Science:

  • Epigenetics and Molecular Biology
  • Developmental Biology
  • Aging Research

Background:

  • The mechanistic link between organismal aging and development remains poorly understood.
  • Chromatin accessibility and transcriptional profiles change with age and during development.

Purpose of the Study:

  • To investigate shared molecular mechanisms connecting aging and development.
  • To identify transcription factor binding site (TFBS) signatures common to both processes.

Main Methods:

  • Profiling age-related chromatin and transcriptional changes in 22 murine cell types.
  • Analyzing data alongside previous mouse and human organismal maturation datasets.
  • Investigating the role of candidate cis-regulatory elements (cCREs) and TFBSs.

Main Results:

  • A common TFBS signature was identified in both aging and development.
  • Early-life cCREs, enriched for cell-type identity TFBSs, lose accessibility during maturation and aging.
  • cCREs gaining accessibility throughout life show reduced cell identity TFBSs and elevated activator protein 1 (AP-1) levels.
  • TF redistribution and H3K27me3 dynamics influence cCRE accessibility and gene expression.

Conclusions:

  • Activator protein 1 (AP-1) mediated chromatin opening disrupts cell identity TFBS-rich cCREs, driving organismal maturation.
  • This mechanism, involving TFBS dynamics and chromatin remodeling, is co-opted during aging.
  • Findings suggest a unified molecular framework for understanding development and aging.
chromatin
development
maturation
polycomb repressive complex 2
redistribution
transcription factors