Three-dimensional genome organization in normal and malignant haematopoiesis.
File(s)
Author(s)
Cuartero, Sergi
Merkenschlager, Matthias
Type
Journal Article
Abstract
PURPOSE OF REVIEW: The three-dimensional organization of the genome inside the nucleus impacts on key aspects of genome function, including transcription, DNA replication and repair. The chromosome maintenance complex cohesin and the DNA binding protein CTCF cooperate to drive the formation of self-interacting topological domains. This facilitates transcriptional regulation via enhancer-promoter interactions, controls the distribution and release of torsional strain, and affects the frequency with which particular translocations arise, based on the spatial proximity of translocation partners. Here we discuss recent insights into the mechanisms of three-dimensional genome organization, their relationship to haematopoietic differentiation and malignant transformation. RECENT FINDINGS: Cohesin mutations are frequently found in myeloid malignancies. Significantly, cohesin mutations can drive increased self-renewal of haematopoietic stem and progenitor cells, which may facilitate the accumulation of genetic lesions and leukaemic transformation. It is therefore important to elucidate the mechanisms that link cohesin to pathways that regulate the balance between self-renewal and differentiation. Chromosomal translocations are key to lymphoid malignancies, and recent findings link three-dimensional genome organization to the frequency and the genomic position of DNA double strand breaks. SUMMARY: Three-dimensional genome organization can help explain genome function in normal and malignant haematopoiesis.
Date Issued
2018-04-26
Date Acceptance
2018-04-01
Citation
Current Opinion in Hematology, 2018, 25 (4), pp.323-328
ISSN
1065-6251
Publisher
Wolters Kluwer Health, Inc.
Start Page
323
End Page
328
Journal / Book Title
Current Opinion in Hematology
Volume
25
Issue
4
Copyright Statement
© 2018 Wolters Kluwer Health, Inc. All rights reserved. This is a non-final version of an article published in final form in Current Opinion in Hematology, https://dx.doi.org/10.1097/MOH.0000000000000436
Sponsor
Wellcome Trust
Medical Research Council (MRC)
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/29702522
Grant Number
099276/Z/12/Z
PO4050659629
Subjects
Science & Technology
Life Sciences & Biomedicine
Hematology
cohesin
genome organization
haematopoiesis
leukaemia
ACUTE MYELOID-LEUKEMIA
COHESIN COMPLEX
CHROMATIN ARCHITECTURE
SUPER-ENHANCERS
TRANSCRIPTIONAL PROGRAM
CHROMOSOME SEGREGATION
CELL DIFFERENTIATION
LINEAGE COMMITMENT
GENE-EXPRESSION
CTCF
Animals
CCCTC-Binding Factor
Cell Cycle Proteins
Cell Differentiation
Cell Nucleus
Cell Transformation, Neoplastic
Chromosomal Proteins, Non-Histone
DNA Breaks, Double-Stranded
DNA Replication
Genome, Human
Hematopoiesis
Hematopoietic Stem Cells
Humans
Leukemia
Neoplasm Proteins
Hematopoietic Stem Cells
Cell Nucleus
Animals
Humans
Leukemia
Cell Transformation, Neoplastic
Cell Cycle Proteins
Neoplasm Proteins
Chromosomal Proteins, Non-Histone
Cell Differentiation
Hematopoiesis
DNA Replication
Genome, Human
DNA Breaks, Double-Stranded
CCCTC-Binding Factor
Immunology
1102 Cardiorespiratory Medicine and Haematology
Publication Status
Published
Coverage Spatial
United States
Date Publish Online
2018-07-01