Trends in Genetics,
Journal Year:
2024,
Volume and Issue:
40(2), P. 160 - 174
Published: Jan. 12, 2024
Recent
imaging
studies
have
captured
the
dynamics
of
regulatory
events
transcription
inside
living
cells.
These
include
factor
(TF)
DNA
binding,
chromatin
remodeling
and
modification,
enhancer-promoter
(E-P)
proximity,
cluster
formation,
preinitiation
complex
(PIC)
assembly.
Together,
these
molecular
culminate
in
stochastic
bursts
RNA
synthesis,
but
their
kinetic
relationship
remains
largely
unclear.
In
this
review,
we
compare
timescales
upstream
steps
(input)
with
kinetics
transcriptional
bursting
(output)
to
generate
mechanistic
models
single
We
highlight
open
questions
potential
technical
advances
guide
future
endeavors
toward
a
quantitative
understanding
regulation.
Science Advances,
Journal Year:
2023,
Volume and Issue:
9(14)
Published: April 5, 2023
In
eukaryotes,
higher-order
chromatin
organization
is
spatiotemporally
regulated
as
domains,
for
various
cellular
functions.
However,
their
physical
nature
in
living
cells
remains
unclear
(e.g.,
condensed
domains
or
extended
fiber
loops;
liquid-like
solid-like).
Using
novel
approaches
combining
genomics,
single-nucleosome
imaging,
and
computational
modeling,
we
investigated
the
behavior
of
early
DNA
replicated
regions
human
cells,
which
correspond
to
Hi-C
contact
with
active
marks.
Motion
correlation
analysis
two
neighbor
nucleosomes
shows
that
form
physically
~150-nm
diameters,
even
regions.
The
mean-square
displacement
between
demonstrates
behave
like
a
liquid
domain
on
~150
nm/~0.5
s
spatiotemporal
scale,
facilitates
accessibility.
Beyond
micrometers/minutes
seems
solid-like,
may
contribute
maintaining
genome
integrity.
Our
study
reveals
viscoelastic
principle
polymer;
locally
dynamic
reactive
but
globally
stable.
Cell,
Journal Year:
2024,
Volume and Issue:
187(2), P. 331 - 344.e17
Published: Jan. 1, 2024
Enhancers
are
distal
DNA
elements
believed
to
loop
and
contact
promoters
control
gene
expression.
Recently,
we
found
diffraction-sized
transcriptional
condensates
at
genes
controlled
by
clusters
of
enhancers
(super-enhancers).
However,
a
direct
function
endogenous
in
controlling
expression
remains
elusive.
Here,
develop
live-cell
super-resolution
multi-color
3D-imaging
approaches
investigate
putative
roles
the
regulation
super-enhancer
Sox2.
In
contrast
enhancer
distance,
find
instead
that
condensate's
positional
dynamics
better
predictor
A
basal
bursting
occurs
when
condensate
is
far
(>1
μm),
but
burst
size
frequency
enhanced
moves
proximity
(<1
μm).
Perturbations
cohesin
local
do
not
prevent
affect
its
enhancement.
We
propose
three-way
kissing
model
whereby
interacts
transiently
with
locus
regulatory
bursting.
Science,
Journal Year:
2023,
Volume and Issue:
380(6652), P. 1357 - 1362
Published: June 29, 2023
Chromosomes
in
the
eukaryotic
nucleus
are
highly
compacted.
However,
for
many
functional
processes,
including
transcription
initiation,
pairwise
motion
of
distal
chromosomal
elements
such
as
enhancers
and
promoters
is
essential
necessitates
dynamic
fluidity.
Here,
we
used
a
live-imaging
assay
to
simultaneously
measure
positions
pairs
their
transcriptional
output
while
systematically
varying
genomic
separation
between
these
two
DNA
loci.
Our
analysis
reveals
coexistence
compact
globular
organization
fast
subdiffusive
dynamics.
These
combined
features
cause
an
anomalous
scaling
polymer
relaxation
times
with
leading
long-ranged
correlations.
Thus,
encounter
loci
much
less
dependent
on
distance
than
predicted
by
existing
models,
potential
consequences
gene
expression.
Annual Review of Biochemistry,
Journal Year:
2023,
Volume and Issue:
92(1), P. 15 - 41
Published: May 3, 2023
SMC
(structural
maintenance
of
chromosomes)
protein
complexes
are
an
evolutionarily
conserved
family
motor
proteins
that
hold
sister
chromatids
together
and
fold
genomes
throughout
the
cell
cycle
by
DNA
loop
extrusion.
These
play
a
key
role
in
variety
functions
packaging
regulation
chromosomes,
they
have
been
intensely
studied
recent
years.
Despite
their
importance,
detailed
molecular
mechanism
for
extrusion
remains
unresolved.
Here,
we
describe
roles
SMCs
chromosome
biology
particularly
review
vitro
single-molecule
studies
recently
advanced
our
understanding
proteins.
We
mechanistic
biophysical
aspects
govern
genome
organization
its
consequences.
Science,
Journal Year:
2023,
Volume and Issue:
382(6672)
Published: Nov. 16, 2023
Cells
remember
their
identities,
in
part,
by
using
epigenetic
marks-chemical
modifications
placed
along
the
genome.
How
can
mark
patterns
remain
stable
over
cell
generations
despite
constant
erosion
replication
and
other
processes?
We
developed
a
theoretical
model
that
reveals
three-dimensional
(3D)
genome
organization
stabilize
memory
as
long
(i)
there
is
large
density
difference
between
chromatin
compartments,
(ii)
modifying
"reader-writer"
enzymes
spread
marks
three
dimensions,
(iii)
are
limited
abundance
relative
to
histone
substrates.
Analogous
an
associative
encodes
neuronal
connectivity,
encoded
3D
network
of
chromosomal
contacts.
Our
provides
unified
account
diverse
observations
key
role
memory.
