Viewing AML through a New Lens: Technological Advances in the Study of Epigenetic Regulation

Epigenetic modifications, such as histone modifications and DNA methylation, are essential for ensuring the dynamic control of gene regulation in every cell type. These modifications are associated with gene activation or repression, depending on the genomic context and specific type of modification...

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Main Authors: Laura C. Godfrey, Alba Rodriguez-Meira
Format: Article
Language:English
Published: MDPI AG 2022-12-01
Series:Cancers
Subjects:
Online Access:https://www.mdpi.com/2072-6694/14/23/5989
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author Laura C. Godfrey
Alba Rodriguez-Meira
author_facet Laura C. Godfrey
Alba Rodriguez-Meira
author_sort Laura C. Godfrey
collection DOAJ
description Epigenetic modifications, such as histone modifications and DNA methylation, are essential for ensuring the dynamic control of gene regulation in every cell type. These modifications are associated with gene activation or repression, depending on the genomic context and specific type of modification. In both cases, they are deposited and removed by epigenetic modifier proteins. In acute myeloid leukemia (AML), the function of these proteins is perturbed through genetic mutations (i.e., in the DNA methylation machinery) or translocations (i.e., MLL-rearrangements) arising during leukemogenesis. This can lead to an imbalance in the epigenomic landscape, which drives aberrant gene expression patterns. New technological advances, such as CRISPR editing, are now being used to precisely model genetic mutations and chromosomal translocations. In addition, high-precision epigenomic editing using dCas9 or CRISPR base editing are being used to investigate the function of epigenetic mechanisms in gene regulation. To interrogate these mechanisms at higher resolution, advances in single-cell techniques have begun to highlight the heterogeneity of epigenomic landscapes and how these impact on gene expression within different AML populations in individual cells. Combined, these technologies provide a new lens through which to study the role of epigenetic modifications in normal hematopoiesis and how the underlying mechanisms can be hijacked in the context of malignancies such as AML.
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spelling doaj.art-31957fd1b24b493f81391e413bf144392023-11-24T10:41:59ZengMDPI AGCancers2072-66942022-12-011423598910.3390/cancers14235989Viewing AML through a New Lens: Technological Advances in the Study of Epigenetic RegulationLaura C. Godfrey0Alba Rodriguez-Meira1Department of Pediatric Oncology, Dana Farber Cancer Institute, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02215, USADepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USAEpigenetic modifications, such as histone modifications and DNA methylation, are essential for ensuring the dynamic control of gene regulation in every cell type. These modifications are associated with gene activation or repression, depending on the genomic context and specific type of modification. In both cases, they are deposited and removed by epigenetic modifier proteins. In acute myeloid leukemia (AML), the function of these proteins is perturbed through genetic mutations (i.e., in the DNA methylation machinery) or translocations (i.e., MLL-rearrangements) arising during leukemogenesis. This can lead to an imbalance in the epigenomic landscape, which drives aberrant gene expression patterns. New technological advances, such as CRISPR editing, are now being used to precisely model genetic mutations and chromosomal translocations. In addition, high-precision epigenomic editing using dCas9 or CRISPR base editing are being used to investigate the function of epigenetic mechanisms in gene regulation. To interrogate these mechanisms at higher resolution, advances in single-cell techniques have begun to highlight the heterogeneity of epigenomic landscapes and how these impact on gene expression within different AML populations in individual cells. Combined, these technologies provide a new lens through which to study the role of epigenetic modifications in normal hematopoiesis and how the underlying mechanisms can be hijacked in the context of malignancies such as AML.https://www.mdpi.com/2072-6694/14/23/5989AMLCRISPRepigenomic editingsingle-cell technologyhematopoiesisleukemia
spellingShingle Laura C. Godfrey
Alba Rodriguez-Meira
Viewing AML through a New Lens: Technological Advances in the Study of Epigenetic Regulation
Cancers
AML
CRISPR
epigenomic editing
single-cell technology
hematopoiesis
leukemia
title Viewing AML through a New Lens: Technological Advances in the Study of Epigenetic Regulation
title_full Viewing AML through a New Lens: Technological Advances in the Study of Epigenetic Regulation
title_fullStr Viewing AML through a New Lens: Technological Advances in the Study of Epigenetic Regulation
title_full_unstemmed Viewing AML through a New Lens: Technological Advances in the Study of Epigenetic Regulation
title_short Viewing AML through a New Lens: Technological Advances in the Study of Epigenetic Regulation
title_sort viewing aml through a new lens technological advances in the study of epigenetic regulation
topic AML
CRISPR
epigenomic editing
single-cell technology
hematopoiesis
leukemia
url https://www.mdpi.com/2072-6694/14/23/5989
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