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Related Concept Videos

Covalently Linked Protein Regulators02:04

Covalently Linked Protein Regulators

Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein.
Epigenetic Regulation01:37

Epigenetic Regulation

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...
Epigenetic Regulation01:46

Epigenetic Regulation

Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
Histone Modification02:32

Histone Modification

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 deacetylase,...
Nucleosome Remodeling02:54

Nucleosome Remodeling

Nucleosomes are the basic units of chromatin compaction. Each nucleosome consists of the DNA bound tightly around a histone core, which makes the DNA inaccessible to DNA binding proteins such as DNA polymerase and RNA polymerase. Hence, the fundamental problem is to ensure access to DNA when appropriate, despite the compact and protective chromatin structure.
Nucleosome remodeling complex
Eukaryotic cells have specialized enzymes called ATP-dependent nucleosome remodeling enzymes. These enzymes...
Spreading of Chromatin Modifications02:25

Spreading of Chromatin Modifications

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 is an enzyme that can...

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Related Experiment Video

Updated: May 16, 2026

Immunostaining for DNA Modifications: Computational Analysis of Confocal Images
09:42

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Published on: September 7, 2017

Mapping Protein Occupancy on DNA with an Unnatural Cytosine Modification.

Ruiyao Zhu1, Christian E Loo2, Christina M Hurley2

  • 1Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.

ACS Chemical Biology
|May 14, 2026
PubMed
Summary
This summary is machine-generated.

Researchers engineered a novel DNA modification, 5-carboxymethylcytosine, to map protein occupancy alongside DNA modifications. This new epigenetic profiling method reveals insights into gene regulation and protein binding patterns.

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Last Updated: May 16, 2026

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Published on: January 20, 2016

Area of Science:

  • Epigenetics
  • Molecular Biology
  • Genomics

Background:

  • The epigenome dynamically regulates gene expression through DNA base modifications and protein-DNA interactions.
  • Concurrent mapping of DNA modifications and protein occupancy is crucial for understanding epigenomic regulation.
  • Existing multimodal mapping methods have limitations, including confounding native modifications and reliance on specific sequencing technologies.

Purpose of the Study:

  • To develop a novel method for multimodal epigenetic profiling by introducing an unnatural DNA base modification.
  • To engineer non-CpG-specific DNA methyltransferases with neomorphic DNA carboxymethyltransferase (CxMTase) activities.
  • To utilize 5-carboxymethylcytosine as a label for protein occupancy in conjunction with DNA modifications.

Main Methods:

  • Engineering of non-CpG-specific DNA methyltransferases to exhibit DNA carboxymethyltransferase activity.
  • Introduction of 5-carboxymethylcytosine as an unnatural DNA base modification.
  • Application of the method to map protein occupancy and DNA methylation patterns.
  • Single-molecule analysis of LexA binding patterns at a bacterial promoter.

Main Results:

  • Successfully engineered DNA methyltransferases with neomorphic CxMTase activities.
  • Demonstrated that DNA carboxymethylation in GpC contexts is compatible with standard epigenetic detection methods.
  • Established the reliability of this method for reporting protein occupancy states.
  • Revealed single-molecule binding patterns of LexA, a bacterial DNA damage response regulator.

Conclusions:

  • Unnatural DNA modifications, like 5-carboxymethylcytosine, can provide novel biological insights.
  • This engineered approach offers a versatile tool for multimodal epigenetic profiling.
  • The method facilitates the concurrent mapping of DNA modifications and protein occupancy, enhancing epigenome interpretation.