Learning from the single cell: A new technique to unravel gene
regulation

Date:
April 1, 2022
Source:
Hubrecht Institute
Summary:
How is the activity of genes regulated by the packaging of DNA? To
answer this question, researchers developed a technique to measure
both gene expression and DNA packaging at the same time.



FULL STORY ==========================================================================
How is the activity of genes regulated by the packaging of DNA? To
answer this question, a technique to measure both gene expression and
DNA packaging at the same time was developed by Franka Rang and Kim
de Luca, researchers from the group of Jop Kind (group leader at the
Hubrecht Institute and Oncode Investigator). This method, EpiDamID,
determines the location of modified proteins around which the DNA is
wrapped. It is important to gather information about these modifications, because they influence the accessibility of DNA, thereby affecting the
gene activity. EpiDamID is therefore valuable for research into the
early development of organisms. The results of the study are published inMolecular Cell on April 1, 2022.


==========================================================================
In order to fit DNA into the nucleus of a cell, it is tightly packed
around nuclear proteins: histones. Depending on the tightness of this
winding, the DNA can be (in)accessible to other proteins. This therefore determines whether the process of gene expression, translation of DNA
into RNA and eventually into proteins, can take place.

DNA packaging determine gene activity The tightness of DNA winding around histones is regulated by the addition of molecular groups, so-called post-translational modifications (PTMs), to the histones. For example,
if certain molecules are added to the histones, the DNA winding is
loosened. This makes the DNA more accessible for certain proteins and
causes the genes in this part of the DNA to become active, or expressed.

Furthermore, proteins that are crucial for gene expression can directly recognize and bind the PTMs. This enables transcription: the process of
DNA copying.

The regulation of gene expression, for instance through PTMs, is also
known as epigenetic regulation. Since all cells in a body have the same
DNA, regulation of gene expression is needed to (de)activate specific
functions in individual cells. For instance, heart muscle cells have
different functions than skin cells, thus require different genes to
be expressed.

Analysis of single cells using EpiDamID To understand how PTMs affect
gene expression, first authors Franka Rang and Kim de Luca designed
a new method to determine the location of the modifications. Using
this approach, called EpiDamID, researchers can analyze single cells,
whereas previous methods were only able to measure a large group of
cells. Analysis on such a small scale results in knowledge on how DNA
winding differs per cell, rather than information on the average DNA
winding of many cells.

EpiDamID is based on DamID, a technique which is used to determine the
binding location of certain DNA-binding proteins. Using EpiDamID, the
binding location of specific PTMs on histone proteins can be detected in
single cells. Compared to others, a great advantage of this technique
is that researchers need very limited material. Furthermore, EpiDamID
can be used in combination with other methods, such as microscopy,
to study regulation of gene expression on different levels.

Future prospects Following the development of this technique, the
Kind group will focus on the role of PTMs from the point of view of developmental biology. Because single cells are analyzed using EpiDamID,
only a limited amount of material is needed to generate enough data. This allows researchers to study the early development of organisms from its
first cell divisions, when the embryo consists of only a few cells.


========================================================================== Story Source: Materials provided by Hubrecht_Institute. Note: Content
may be edited for style and length.


========================================================================== Journal Reference:
1. Franka J. Rang, Kim L. de Luca, Sandra S. de Vries, Christian
Valdes-
Quezada, Ellen Boele, Phong D. Nguyen, Isabel Guerreiro, Yuko Sato,
Hiroshi Kimura, Jeroen Bakkers, Jop Kind. Single-cell profiling of
transcriptome and histone modifications with EpiDamID. Molecular
Cell, 2022; DOI: 10.1016/j.molcel.2022.03.009 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/04/220401122200.htm

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