Asset Details
Do you wish to reserve the book?
Mutational synergy during leukemia induction remodels chromatin accessibility, histone modifications and three-dimensional DNA topology to alter gene expression
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
Mutational synergy during leukemia induction remodels chromatin accessibility, histone modifications and three-dimensional DNA topology to alter gene expression
Do you wish to request the book?
Mutational synergy during leukemia induction remodels chromatin accessibility, histone modifications and three-dimensional DNA topology to alter gene expression
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
Mutational synergy during leukemia induction remodels chromatin accessibility, histone modifications and three-dimensional DNA topology to alter gene expression
2021
Overview
Altered transcription is a cardinal feature of acute myeloid leukemia (AML); however, exactly how mutations synergize to remodel the epigenetic landscape and rewire three-dimensional DNA topology is unknown. Here, we apply an integrated genomic approach to a murine allelic series that models the two most common mutations in AML:
Flt3
-
ITD
and
Npm1c
. We then deconvolute the contribution of each mutation to alterations of the epigenetic landscape and genome organization, and infer how mutations synergize in the induction of AML. Our studies demonstrate that
Flt3-ITD
signals to chromatin to alter the epigenetic environment and synergizes with mutations in
Npm1c
to alter gene expression and drive leukemia induction. These analyses also allow the identification of long-range
cis
-regulatory circuits, including a previously unknown superenhancer of
Hoxa
locus, as well as larger and more detailed gene-regulatory networks, driven by transcription factors including PU.1 and IRF8, whose importance we demonstrate through perturbation of network members.
Mice bearing mutations in
Flt3-ITD
and
Npm1c
, which are commonly found in acute myeloid leukemia, are used to characterize the cooperative effects of these cancer drivers on the cellular epigenome and three-dimensional genome conformation during tumor development.
Publisher
Nature Publishing Group US,Nature Publishing Group
Subject
/ Animal Genetics and Genomics
/ Animals
/ Biomedical and Life Sciences
/ Cancer
/ Chromatin Assembly and Disassembly - genetics
/ DNA
/ Enhancer Elements, Genetic - genetics
/ fms-Like Tyrosine Kinase 3 - metabolism
/ Gene Expression Regulation, Leukemic
/ Genomes
/ Histones
/ Humans
/ Leukemia
/ Leukemia, Myeloid, Acute - genetics
/ Mice
/ Mutation
/ Nuclear Proteins - metabolism
/ Post-translational modification
/ Principal Component Analysis
/ Principal components analysis
/ Protein Processing, Post-Translational
/ Topology
