Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Histone Modification02:32

Histone Modification

13.5K
The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone...
13.5K
Spreading of Chromatin Modifications02:25

Spreading of Chromatin Modifications

8.3K
The histone proteins in the nucleosomes are post-translationally modified (PTM) to increase or decrease access to DNA. The commonly observed PTMs are methylation, acetylation, phosphorylation, and ubiquitination of lysine amino acids in the histone H3 tail region. These histone modifications have specific meaning for the cell. Hence, they are called "histone code". The protein complex involved in histone modification is termed as "reader-writer" complex.
Writers
The writer...
8.3K
Histone Variants at the Centromere02:30

Histone Variants at the Centromere

4.4K
Histone variants are the histone proteins with structural and sequence variations. These variants may be regarded as “mutant” forms that replace their canonical histone counterparts in the nucleosomes. Specific post-translational modifications on the histone variants enable further chromatin complexity and regulate tissue-specific gene expression. The most common histone variants are from histone H2A, H2B, and linker histone H1 families. However, several variants of histone H3...
4.4K
Chromatin Modification in iPS Cells01:32

Chromatin Modification in iPS Cells

1.7K
Chromatin modification alters gene expression; therefore, scientists can add histone-modifying enzymes, histone variants, and chromatin remodeling complexes to somatic cells to aid reprogramming into pluripotent stem (iPS) cells.
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
1.7K
Co-activators and Co-repressors02:04

Co-activators and Co-repressors

7.4K
Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
7.4K
Epigenetic Regulation01:37

Epigenetic Regulation

3.1K
Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
3.1K

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Two-dimensional assessments of civility and incivility at work.

BMC psychology·2026
Same author

Myeloid-avid mammalian target of rapamycin-inhibiting nanobiologic attenuates allograft fibrosis after lung transplantation.

American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons·2026
Same author

MYC pathway reprogramming through a TIP60 coactivator switch in neuroendocrine lineage transition in prostate cancer.

bioRxiv : the preprint server for biology·2026
Same author

CDCP1 Deletion Protects Against Pressure Overload-Induced Cardiac Dysfunction and Fibrosis in Mice.

Research square·2026
Same author

Genotype epigenome phenotype integration reveals peripheral immune contributions to type I bipolar disorder.

Nature communications·2026
Same author

PEPN1924, A Phase II Study of Trastuzumab Deruxtecan in Patients With Recurrent Human Epidermal Growth Factor Receptor 2+ Osteosarcoma: A Children's Oncology Group Pediatric Early-Phase Clinical Trial Network Study.

JCO oncology advances·2026

Related Experiment Video

Updated: Aug 9, 2025

Author Spotlight: Epigenetic Modifications and Metabolic Rewiring as Targets for Cancer Therapy
07:20

Author Spotlight: Epigenetic Modifications and Metabolic Rewiring as Targets for Cancer Therapy

Published on: October 18, 2024

578

MacroH2A histone variants modulate enhancer activity to repress oncogenic programs and cellular reprogramming.

Wazim Mohammed Ismail1,2, Amelia Mazzone1,2, Flavia G Ghiraldini3,4

  • 1Division of Experimental Pathology, Department of Lab Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.

Communications Biology
|February 23, 2023
PubMed
Summary
This summary is machine-generated.

Histone variants macroH2A mark inactive enhancers (macro-bound enhancers) that maintain cell identity. Their reactivation links to breast cancer oncogenic programs and stem cell activity.

More Related Videos

Global Level Quantification of Histone Post-Translational Modifications in a 3D Cell Culture Model of Hepatic Tissue
08:12

Global Level Quantification of Histone Post-Translational Modifications in a 3D Cell Culture Model of Hepatic Tissue

Published on: May 5, 2022

4.0K
Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers
10:28

Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers

Published on: September 20, 2018

6.5K

Related Experiment Videos

Last Updated: Aug 9, 2025

Author Spotlight: Epigenetic Modifications and Metabolic Rewiring as Targets for Cancer Therapy
07:20

Author Spotlight: Epigenetic Modifications and Metabolic Rewiring as Targets for Cancer Therapy

Published on: October 18, 2024

578
Global Level Quantification of Histone Post-Translational Modifications in a 3D Cell Culture Model of Hepatic Tissue
08:12

Global Level Quantification of Histone Post-Translational Modifications in a 3D Cell Culture Model of Hepatic Tissue

Published on: May 5, 2022

4.0K
Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers
10:28

Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers

Published on: September 20, 2018

6.5K

Area of Science:

  • Epigenetics
  • Molecular Biology
  • Cancer Biology

Background:

  • Active enhancers are typically marked by accessible chromatin and H3 lysine 27 acetylation (H3K27ac).
  • The function of cis-regulatory elements lacking H3K27ac remains largely unknown, except for poised enhancers and putative silencers.
  • Understanding regulatory elements is crucial for deciphering gene regulation in normal development and disease.

Purpose of the Study:

  • To investigate the role of histone variants, specifically macroH2A, at cis-regulatory elements lacking H3K27ac.
  • To define and characterize a novel class of enhancers termed 'macro-Bound Enhancers'.
  • To explore the functional significance of macro-bound enhancers in cell identity, cancer, and stem cell activity.

Main Methods:

  • Chromatin immunoprecipitation (ChIP) to identify macroH2A localization at enhancers.
  • Analysis of H3K27ac marks to distinguish active from inactive enhancers.
  • Single-cell epigenomic profiling to assess enhancer activity in stem cells.
  • Correlation analysis between macroH2A, BRD4 occupancy, and gene expression in cancer.

Main Results:

  • MacroH2A variants were found at enhancer elements lacking H3K27ac in a cell type-specific manner, defining them as 'macro-Bound Enhancers'.
  • These macro-bound enhancers play a role in maintaining cell identity by remaining inactive.
  • Reactivation of macro-bound enhancers is linked to oncogenic programs in breast cancer.
  • MacroH2A2 acts as a negative regulator of BRD4 chromatin occupancy.
  • MacroH2A deficiency in mammary stem cells increases the activity of transcription factors associated with stem cell function.

Conclusions:

  • MacroH2A variants identify a novel class of inactive enhancers (macro-bound enhancers) critical for maintaining cell identity.
  • Dysregulation of macro-bound enhancers, particularly their reactivation, is associated with breast cancer progression.
  • MacroH2A plays a repressive role, influencing BRD4 occupancy and potentially impacting oncogenic pathways.
  • Targeting macroH2A or macro-bound enhancers may offer new therapeutic strategies for cancer and stem cell-related disorders.