An important transcription factor "FoxH1" mechanism of action

Transcription factors are proteins
that interact with DNA to regulate the function of certain genes.
In general, a transcription factor binds to several regions in the genome because it coordinates complex cellular responses, which require activation or inhibition
of several genes.
FoxH1 is an essential transcription factor during embryonic development, and in adults, it has been linked to
the progression of lung cancer and certain types of leukemia.

Scientists at the Barcelona Institute, led by ICREA researcher Dr.
Maria J.
Macias, have described in detail the mechanism
by which the FoxH1 factor binds to DNA at the atomic scale.
In other words, they described and developed a 3D model that reproduces how FoxH1 binds to specific points in the genome to perform its functions
.

"FoxH1 is of interest to our lab and others because it plays a very important role
in embryonic development and the development of some tumors.
Although its relevance has been known for a long time, it has only now been possible to describe its binding to DNA," explains
Dr.
Macías, head of the Laboratory for the Characterization of Macromolecular Assembly Structures at the Barcelona Institute.
She added: "The structural details we found in this work may enable the development of specific molecules that interact with FoxH1 and, in the future, potentially lead to drugs
to treat diseases in which this protein plays a key role.
"

An unusual binding mechanism

FoxH1 belongs to a very large family of transcription factors called FOX, but it has some characteristics
.
The property that attracted the researchers' attention was its ability to bind
to DNA even when it was compacted and protected by the nucleosome structure.

In order to bind to DNA and perform their regulatory functions, most transcription factors need this molecule to unfold, thus exposing themselves
.
Transcription factors like FoxH1 that bind to compressed DNA are called precursor factors
.

Dr.
Eric Aragon said: "In addition, the DNA sequence that FoxH1 binds to is different from the sequence recognized by other transcription factors in its family, so we wanted to understand the structural characteristics
that allow FoxH1 to acquire these very specific properties.
"

Dr.
Radoslaw Pluta, a postdoctoral researcher in the same lab, concluded: "We are pleased to be able to resolve these structures at 1 resolution because it allows us to describe the interactions
in great detail.
"

Future work in the lab will focus on characterizing the interaction
between FoxH1 and nucleosomes at the atomic scale.