Related Experiment Video
Updated: Jul 3, 2026
08:49
A Multilabel Single Molecule Localization Microscopy Protocol for Investigation of Chromatin in the Dense Nuclear Environment
Published on: June 5, 2026
Beyond The Nucleus: Translating Engineered Protein Localization To Chromatin Modifying Enzymes
Zanir Hirani1, Rabindra Tirouvanziam1,2,3, Karmella A Haynes1
1Wallace H. Coulter Department of Biomedical Engineering, Emory University, Atlanta, GA 30322, USA.
Current Opinion in Biomedical Engineering
|July 2, 2026
Summary
Chromatin-modifying enzymes (CMEs) have non-canonical roles outside the nucleus. Engineering strategies can control CME localization for disease research and therapeutics.
Area of Science:
- Molecular Biology
- Epigenetics
- Cell Biology
Background:
- Chromatin-modifying enzymes (CMEs) are traditionally studied within the nucleus for gene regulation.
- Emerging evidence reveals significant non-canonical functions of CMEs in cytoplasm, mitochondria, and plasma membrane, impacting disease and cell phenotypes.
Purpose of the Study:
- To review engineering approaches for controlling protein localization, applicable to CMEs.
- To explore how these tools can advance understanding of CME functions and disease mechanisms.
Main Methods:
- Survey of natural regulatory mechanisms (nuclear import/export, mechanical force).
- Overview of engineering strategies: synthetic signals, RNA editing (SNAP-ADAR), small molecules, nanobodies, optogenetics, inducible condensates, protease cleavage, secondary messenger coupling.
Main Results:
- Diverse engineering tools exist for precise protein relocalization.
- Application of these tools to CMEs is largely unexplored but holds significant potential.
Conclusions:
- Controlling CME localization via engineering offers novel avenues for disease mechanism decoding.
- Future applications promise to deepen understanding of epigenetics and CME roles in health and disease.
Related Concept Videos
02:22Regulated mRNA Transport
In eukaryotes, transcription and translation are compartmentalized; an mRNA is first synthesized in the nucleus and then selectively transported to the cytoplasm for protein synthesis. Before transport, a pre-mRNA undergoes several steps of post-transcriptional modifications including splicing, 5' capping, and the addition of a poly-adenine tail. Various proteins bind to the pre-mRNA during these modifications. The mRNA transport takes place with the help of multiple proteins playing specific...
01:34Nuclear Protein Sorting
Nuclear protein sorting is the selective trafficking of histones, polymerases, gene regulatory proteins into the nucleus and exporting RNAs and ribosomes to the cytosol. It is a tightly controlled process that regulates gene expression within a cell.
Proteins targeted to the nucleus carry nuclear localization signals or NLS recognized by import receptors in the cytosol. Similarly, proteins with nuclear export signals are recognized by export receptors. Import and export receptors are...
Proteins targeted to the nucleus carry nuclear localization signals or NLS recognized by import receptors in the cytosol. Similarly, proteins with nuclear export signals are recognized by export receptors. Import and export receptors are...
02:35Chromatin Position Affects Gene Expression
Chromatin is the massive complex of DNA and proteins packaged inside the nucleus. The complexity of chromatin folding and how it is packaged inside the nucleus greatly influences access to genetic information. Generally, the nucleus' periphery is considered transcriptionally repressive, while the cell's interior is considered a transcriptionally active area.
Topologically Associated Domains (TADs)
The 3-dimensional positioning of chromatin in the nucleus influences the timing and level of...
Topologically Associated Domains (TADs)
The 3-dimensional positioning of chromatin in the nucleus influences the timing and level of...
01:45Regulation of Nuclear Protein Sorting
Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
01:42Nuclear Export
The nucleus restricts several proteins within and allows others to pass. The restricted proteins possess a nuclear retention sequence or NRS, anchoring them to the nuclear lamins and preventing their transport to the cytosol. The non-restricted proteins, after their synthesis, are transported to their site of action, such as the cytosol or other organelles, with the help of nuclear export signals or NES.
NES are of three types- the canonical 10-residue long leucine-rich signal and other...
NES are of three types- the canonical 10-residue long leucine-rich signal and other...
02:31Nuclear Export of mRNA
Before mRNAs are exported to the cytoplasm, it is crucial to check each mRNA for structural and functional integrity. Eukaryotic cells use several different mechanisms, collectively known as mRNA surveillance, to look for irregularities in mRNAs. Irregular or aberrant mRNA are rapidly degraded by various enzymes. If a defective mRNA escapes the surveillance, it would be translated into a protein which would either be non-functional or not function properly. One of the primary irregularities in...