Processivity and specificity of histone acetylation by the male-specific lethal complex
Nucleic Acids Research,
Год журнала:
2024,
Номер
52(9), С. 4889 - 4905
Опубликована: Фев. 26, 2024
Acetylation
of
lysine
16
histone
H4
(H4K16ac)
stands
out
among
the
modifications,
because
it
decompacts
chromatin
fiber.
The
metazoan
acetyltransferase
MOF
(KAT8)
regulates
transcription
through
H4K16
acetylation.
Antibody-based
studies
had
yielded
inconclusive
results
about
selectivity
to
acetylate
N-terminus.
We
used
targeted
mass
spectrometry
examine
activity
in
male-specific
lethal
core
(4-MSL)
complex
on
nucleosome
array
substrates.
This
is
part
Dosage
Compensation
Complex
(DCC)
that
activates
X-chromosomal
genes
male
Drosophila.
During
short
reaction
times,
acetylated
efficiently
and
with
excellent
selectivity.
Upon
longer
incubation,
enzyme
progressively
lysines
12,
8
5,
leading
a
mixture
oligo-acetylated
H4.
Mathematical
modeling
suggests
recognizes
acetylates
high
selectivity,
but
remains
substrate-bound
continues
more
N-terminal
processive
manner.
4-MSL
lacks
non-coding
roX
RNA,
critical
component
DCC.
Remarkably,
addition
RNA
non-specifically
suppressed
oligo-acetylation
favor
specific
Because
destabilizes
MSL-nucleosome
interaction
vitro
we
speculate
accelerates
enzyme-substrate
turn-over
vivo,
thus
limiting
processivity
MOF,
thereby
increasing
Язык: Английский
KAT8 beyond Acetylation: A Survey of Its Epigenetic Regulation, Genetic Variability, and Implications for Human Health
Genes,
Год журнала:
2024,
Номер
15(5), С. 639 - 639
Опубликована: Май 17, 2024
Lysine
acetyltransferase
8,
also
known
as
KAT8,
is
an
enzyme
involved
in
epigenetic
regulation,
primarily
recognized
for
its
ability
to
modulate
histone
acetylation.
This
review
presents
overview
of
emphasizing
biological
functions,
which
impact
many
cellular
processes
and
range
from
chromatin
remodeling
genetic
regulation.
In
model
systems,
KAT8’s
acetylation
H4
lysine
16
(H4K16)
critical
structure
modification,
influences
gene
expression,
cell
proliferation,
differentiation,
apoptosis.
Furthermore,
this
summarizes
the
observed
variability
within
KAT8
gene,
underscoring
implications
various
single
nucleotide
polymorphisms
(SNPs)
that
affect
functional
efficacy
are
linked
diverse
phenotypic
outcomes,
ranging
metabolic
traits
neurological
disorders.
Advanced
insights
into
structural
biology
reveal
interaction
with
multiprotein
assemblies,
such
male-specific
lethal
(MSL)
non-specific
(NSL)
complexes,
regulate
a
wide
transcriptional
activities
developmental
functions.
Additionally,
focuses
on
roles
homeostasis,
stem
identity,
DNA
damage
repair,
immune
response,
highlighting
potential
therapeutic
target.
The
health
disease,
evidenced
by
recent
studies,
affirm
importance
physiology
human
pathology.
Язык: Английский