A
histone is a small protein found in our cells that helps organize and package DNA, which is the genetic material of our bodies. It acts like a spool for DNA, allowing it to be tightly wound and packed into a compact structure called chromatin.
Histones play a crucial role in regulating genes and determining how our cells function and develop.
Full definition
Worden, along with his sponsor Cynthia Wolberger, Ph.D., examines how the decision to «turn on» or «turn off» genes is determined by a highly coordinated series of events that rely on the chemical modification
of histone proteins.
Review Publication - Mechanisms of
Histone Deacetylase Inhibitor - Regulated Gene Expression in Cancer Cells
To examine the chromatin structure of rice centromere 8, Nagaki et al. [6] used ChIP - PCR with antibodies against two different covalent modifications of the canonical H3
histone protein (rather than the centromere - specific CenH3): dimethylation on lysine 9 (dimethyl - K9), which has been shown to be enriched in heterochromatic regions, and dimethyl - K4, which is present in euchromatic portions of the chromosome.
When the researchers administered drugs
called histone deacetylase inhibitors (HDACs)-- which promote acetylation — to mice, they had the same effect as environmental stimulation.
The decrease
in histone methyltransferase EZH2 in response to fluid shear stress alters endothelial gene expression and promotes quiescence.
Therefore, deleting the portion of the chromosome with
histone genes in order to replace them with a modified one would wind up deleting other genes vital for survival.
Mutations of
histone acetylation genes (category II) were found in EP300 (encoding H3K18 acetyltransferase, 10/125 patients, 8.0 %) and in CREBBP (encoding H3K18 acetyltransferase, 5/125 patients, 4.0 %).
Our ground - breaking work has created a paradigm shift in cancer with the identification of
histone mutations in human disease and we hope to translate these findings into optimal detection and therapeutic possibilities at the bedside.
The role of
histone codes and DNA methylation in silencing tumor suppressor genes, Cancer Cell 3:89 - 95, 2003.
Neuronal developmental gene and miRNA signatures induced
by histone deacetylase inhibitors in human embryonic stem cells.
HMT family of proteins consist of enzymes that methylate lysine or arginine residues
on histone tails as well as other proteins.
Without an adequate supply of the S - adenosyl methionine, regulation by
histone methylation — and therefore correct gene expression — can not take place.
A preclinical study in mice published by Cell Press January 16th in the journal Cell reveals that drugs known
as histone deacetylase inhibitors (HDACis) can enhance the brain's ability to permanently replace old traumatic memories with new memories, opening promising avenues for the treatment of posttraumatic stress disorder (PTSD) and other anxiety disorders.
Epigenetic factors modify
histone tails by e.g. transferring methyl or acetyl groups on lysine side chains.
Kasinath and Poepsel, have now solved the structure of PRC2, which provides a framework to understand how this complex is regulated to
modify histone proteins.
DNA scaffolding has a hierarchy that ranges from beads - on - a-string, where a strand of DNA is wrapped
around histone proteins to form a nucleosome, to topological associating domains akin to DNA balls containing multiple DNA loops interacting with various regulatory elements, to highly condensed chromosomes.
All but one of these was derived
from histone proteins, which are known to have antimicrobial activities.
But many biologists had searched in vain for enzymes that did the opposite, leaving them wondering if these so - called
histone demethylases even existed.
One of my favorite papers from this year was the landmark publication of the NIH Epigenomics Roadmap Consortium, which profiled 111 primary human tissues and cell types
for histone modification patterns, DNA accessibility, DNA methylation, and gene expression.
A variety of
histone chaperones are involved in these dynamics, but how these activities are integrated in this process remains largely unclear.
Rea, S.; Eisenhaber, F.; O'Carroll, D.; Strahl, B. D.; Sun, Z. W.; Schmid, M.; Opravil, S.; Mechtler, K.; Ponting, C. P.; Allis, C. D.; Jenuwein, T. Regulation of chromatin structure by site -
specific histone H3 methyltransferases.
The Cac2 subunit is essential for productive
histone binding and nucleosome assembly in CAF - 1.
Li Y, Wen H, Xi Y, Tanaka K, Wang H, Peng D, Ren Y, Jin Q, Dent SYR., Li W, Li H, Shi X (2014) AF9 YEATS Domain
Links Histone Acetylation to DOT1L - Mediated H3K79 Methylation.
Researchers led by St. Jude Children's Research Hospital scientists have worked out how a crucial cancer - related protein, a «
histone writer» called Ezh2, plays a role in suppressing as well as driving the most aggressive form of the brain tumor medulloblastoma.
Using the five
core histone methylation marks I've just described, the authors trained a chromatin state model that classified every region into one of 15 states:
«In this study we successfully
targeted histone acetylation with a bromodomain inhibitor, a compound that is currently in studies for different types of advanced cancers in adults, but has never been studied in DIPG,» said senior author Ali Shilatifard, PhD, Chair of Department of Biochemistry and Molecular Genetics and Robert Francis Furchgott Professor at Northwestern University Feinberg School of Medicine.
In this study, the researchers focused on
histone crotonylation, an epigenetic mechanism that modifies the proteins that package DNA, affecting gene expression.
Her laboratory studies the impact of cellular metabolism on the epigenome, focusing on the role of acetyl - CoA in
regulating histone acetylation.
The tumor suppressor BAP1 associates with ASXL1 / 2 to form the core Polycomb complex PR - DUB, which catalyzes the removal of mono - ubiquitin from several substrates including
histone H2A.
Above, individual spots represent
acetylated histones in a brain region called the hippocampus.
«Our findings highlight the remarkable impact that subtle structural differences
between histone H3 variants has in the global landscape of epigenetics,» says Couture.
One way in
which histone modifications elicit biological responses is by being recognised by specific proteins, so - called «readers.»
Histones play an important role for the activity of our genes, as they contain information that can turn on or off genes.
Latham JA, Chosed RJ, Wang S, Dent SY (2011) Chromatin signaling to kinetochores: transregulation of Dam1 methylation by
histone H2B ubiquitination.
SMN Is Essential for the Biogenesis of U7 Small Nuclear Ribonucleoprotein and 3 ′ - End Formation of
Histone mRNAs.
Currently, enhancers can be identified through chromatin - based assays, such as ChIP - seq, which predict enhancer elements indirectly based on the enhancer's association with specific epigenomic marks, such as transcription factors or molecular tags on DNA -
associated histone proteins.
«In those samples, we were able to disrupt the HIV silencing by
inducing histone crotonylation.»
In addition to reevaluating
how histones control gene activation, the study also reports a new mechanism of PARP1 regulation.
Another study suggests that transient hyperglycemia could
alter histone methylation, leading to diabetic complications.
To alter DNA modifications, researchers used blunt tools
like histone deacetylases, but targeted epigenetic modification was impossible.