Emerging roles for chromatin as a signal integration and storage platform
Open accessAbstract
Cells of a multicellular organism, all containing nearly identical genetic information, respond to differentiation cues in variable ways. In addition, cells are plastic, able to execute their specialized function while maintaining the ability to adapt to environmental changes. This is achieved through multiple mechanisms, including the direct regulation of chromatin-based processes in response to stimuli. How signal transduction pathways directly communicate with chromatin to change the epigenetic landscape is poorly understood. The preponderance of covalent modifications on histone tails coupled with a relatively small number of functional outputs raises the possibility that chromatin acts as a site of signal integration and storage.
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In human disease, stress-induced signaling converges in the nucleus, where chromatin receives, processes and amplifies upstream inputs, leading to altered gene expression, maladaptive cell state transitions and organ dysfunction.
“In human disease, stress-induced signaling converges in the nucleus, where chromatin receives, processes, and amplifies upstream inputs, ultimately leading to altered gene expression, maladaptive cell state transitions and organ dysfunction1.”
From Chromatin remodelling drives immune cell–fibroblast communication in heart failure (2024) · cites this paper as [1]
The Introduction (page not available) describes signaling reaching the nucleus and changing gene expression, while “Signal integration on histones” describes chromatin integrating multiple inputs into a transcriptional response. The Conclusion and perspectives links epigenetic signaling to disease and gives cancer-cell state changes as an example. It does not establish the full claimed chain from stress-induced signaling through chromatin amplification to organ dysfunction; its account of integration is partly speculative. (LLM, conf=0.86)
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When Metabolism and Epigenetics Converge
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- Authors
- Badeaux, A. I., & Shi, Y.
- Affiliations
- Boston Children's Hospital (US)
- Corresponding author
- Badeaux, Aimee I.
- Shi, Yang
- ORCID
- Shi, Yang
- Venue
- Nature Reviews Molecular Cell Biology
- Published
- 2013-03-22
- Volume
- 14
- Issue
- 4
- Pages
- 211-224
- ISSN
- 1471-0072 (ISSN-L)
- 1471-0080
- PMC
- PMC4082330
- OpenAlex
- W1977281942
- Cited by
- 291
- References
- 134
- Citations by year
- 2026: 7 · 2025: 13 · 2024: 17 · 2023: 17 · 2022: 10 · 2021: 19 · 2020: 12 · 2019: 25 · 2018: 18 · 2017: 24 · 2016: 38 · 2015: 36 · 2014: 38 · 2013: 17
- FWCI
- 4.11
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Reviews Molecular Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- American Cancer Society
- National Institutes of Health
- National Institute of Mental Health (R01MH096066, MH096066)
- National Cancer Institute (R01CA118487, CA118478)
- National Institute of General Medical Sciences (GM058012, GM071044, R01GM058012, R01GM071044)
- National Institute of Neurological Disorders and Stroke (T32NS007473)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Keywords
- chromatin, signal transduction, histone modifications, epigenetic memory, signal integration, gene expression regulation, cell differentiation, cellular plasticity, epigenetic landscape
- MeSH terms
- Cell Communication, Chromatin, Histones, Humans, Methylation, Models, Genetic, Signal Transduction, Epigenesis, Genetic
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