Every cancer starts with a single cell, and Jackson Laboratory (JAX) researchers have found a precise and reliable way — whole - genome profiling
of open chromatin — to identify the kind of cell that leads to a given case of leukemia, a valuable key to cancer prognosis and outcome.
Regulatory elements tend to occur in regions
of open chromatin (euchromatin), where they are accessible to transcription factors and other proteins.
The DNase I restriction enzyme cleaves regions
of open chromatin, and it preferentially does so at places where, nearby, there are non-histone proteins bound to DNA.
It was previously believed that embryonic stem cells had lots
of open chromatin (euchromatin), but this was not a proven theory.
This is consistent with a model in which DNA gain and loss results in turnover or «churning» in regulatory element dense regions
of open chromatin, where interruption of regulatory elements is selected against.
The application of next - gen sequencing to RNA libraries (RNA - Seq), chromatin immunoprecipitates (CHiP - Seq), bisulfite - treated DNA, and regions
of open chromatin (DNAse - Seq) makes it possible to interrogate many aspects of the genome in high - throughput fashion.
Having established some understanding
of the open chromatin landscape in healthy mice, the researchers now hope to figure out how these relationships change with disease states.
Not exact matches
He said that the loss
of Set2 keeps the
chromatin in a more
open state — not as compact as normal.
A large cast
of biomolecular players finesses different swaths
of this contorted
chromatin into more closed or
open shapes.
Depending on the tissue type and what jobs that tissue is doing, distinct portions
of DNA are unspooled to become available for activity through a structure called
open chromatin, said Gregory Crawford, an associate professor
of pediatrics and expert on gene expression.
But what they found is that the host chooses which
chromatin regions are
opened to make genes available for use in each region
of the intestine.
The researchers went into this study expecting to find that the microbes signaled the host to
open up areas
of chromatin to activate gene expression in the gut.
She likens TCF - 1 to an icebreaker ship that initially
opens the ice (condensed, closed
chromatin) and keeps a path available for other ships (other transcription factors that work in later stages
of development) to steam through the now -
open water (unwound
chromatin).
«It has become very clear that the
opening up or tightening
of chromatin, to expose or hide genes in our chromosomes, plays a role in cancer progression,» dos Santos says.
Neocentromeres have also been shown to harbor expressed genes [13], and the rice finding shows that the
chromatin structure
of both plant and mammalian CenH3 - binding domains is
open and accessible to the transcriptional machinery.
«Although histone 1 is key component
of chromatin - the form in which DNA is packaged inside the cell nucleus through the action
of histones -, there are still many questions
open regarding this molecule,» says Ferran Azorín.
It turns out, as depicted by the model, that Ascl1 acts as a pioneer transcription factor that is capable
of opening closed
chromatin, and recruit the other factors to induce neuronal gene transcription.
What we think is that perhaps SOX2 is, even on a greater scale than Ascl1, capable
of opening closed
chromatin and thereby facilitating reprogramming.
Opening the way to accurately profile the
chromatin states
of in vivo stem cells, lineage progenitors and other scarce cell populations.
Chromatin's new identity as a non-transcriptional signaling agent
opens up a plethora
of research avenues.
TCF - 1 is like an icebreaker ship that initially
opens the ice (condensed, closed
chromatin) and keeps a path available for other ships (other transcription factors that work in later stages
of development) to steam through the now -
open water (unwound
chromatin).
Key to these functions is its role as a sort
of chromatin control panel — a
chromatin «factor,» in research argot — regulating those
openings, closings and shape - changings.
At sites
of UV damage, E2F1 recruits the histone acetyltransferase GCN5, which acetylates histone H3K9 in order to
open chromatin structure and increase accessibility to the damaged site by the DNA repair machinery.
However, the paper suggests this is due to epigenetic effects and
chromatin remodelling,
opening up a potential for epigenetic modulators in future treatment
of RA.
ES cell
chromatin is
open at a global level [3], and the stem cells express high levels
of chromatin remodeling factors.
Trowbridge hypothesized that analyzing
open chromatin in bulk tumor cells could provide a possible improved method to identify cancer cell
of origin because
of the cell - type specificity
of chromatin structure.