Related Experiment Video

Updated: Mar 7, 2026

Investigation of the Transcriptional Role of a RUNX1 Intronic Silencer by CRISPR/Cas9 Ribonucleoprotein in Acute Myeloid Leukemia Cells
09:16

Investigation of the Transcriptional Role of a RUNX1 Intronic Silencer by CRISPR/Cas9 Ribonucleoprotein in Acute Myeloid Leukemia Cells

Published on: September 1, 2019

8.1K

Small genomic insertions form enhancers that misregulate oncogenes

Brian J Abraham1, Denes Hnisz1, Abraham S Weintraub1,2

  • 1Whitehead Institute for Biomedical Research, 455 Main Street, Cambridge, Massachusetts 02142, USA.

Nature Communications
|February 10, 2017
PubMed

Insights

Researchers identified small insertion variants in non-coding DNA, specifically near oncogenes. One insertion created an active enhancer, driving LMO2 oncogene expression in leukemia, offering new insights into cancer development.

Area of Science:

  • Genomics
  • Cancer Biology
  • Molecular Oncology

Background:

  • Non-coding DNA variations contribute to tumorigenesis but their functional roles are unclear.
  • Somatic insertions in non-coding regions are poorly understood due to sequencing challenges.

Purpose of the Study:

  • To develop a method for identifying enhancer-associated small insertion variants.
  • To investigate the functional impact of these variants in human cancers.

Main Methods:

  • Utilized ChIP-seq (Chromatin Immunoprecipitation sequencing) to enrich for enhancer DNA.
  • Employed computational analysis with multiple DNA alignment procedures.
  • Analyzed 102 tumor cell genomes.

Main Results:

  • Identified frequent small insertions in enhancer DNA near known oncogenes.
  • Discovered a somatic insertion in leukemia genomes that forms an active enhancer.
  • This enhancer drives the expression of the LMO2 oncogene.

Conclusions:

  • The developed approach effectively identifies enhancer-associated small insertion variants.
  • These variants can functionally contribute to tumorigenesis by altering oncogene expression.
  • Provides a basis for studying these abnormalities in various human cancers.

More Related Videos

Promoter Capture Hi-C: High-resolution, Genome-wide Profiling of Promoter Interactions10:16

Promoter Capture Hi-C: High-resolution, Genome-wide Profiling of Promoter Interactions

Published on: June 28, 2018

33.6K
Dissection of Enhancer Function Using Multiplex CRISPR-based Enhancer Interference in Cell Lines10:46

Dissection of Enhancer Function Using Multiplex CRISPR-based Enhancer Interference in Cell Lines

Published on: June 2, 2018

9.9K

Related Concept Videos

Cancer-Critical Genes I: Proto-oncogenes01:33

Cancer-Critical Genes I: Proto-oncogenes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
11.7K
Epigenetic Regulation01:37

Epigenetic Regulation

Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
4.0K
Epigenetic Regulation01:46

Epigenetic Regulation

Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
34.1K
Induced Pluripotent Stem Cells01:06

Induced Pluripotent Stem Cells

Stem cells are undifferentiated cells that divide and produce different cell types. Ordinarily, cells that have differentiated into a specific cell type are terminally differentiated; however, scientists have found a way to reprogram these mature cells so that they dedifferentiate and return to an unspecialized, proliferative state. These cells are pluripotent like embryonic stem cells—able to produce all cell types—and are called induced pluripotent stem cells (iPSCs).
Somatic...
5.7K
Non-LTR Retrotransposons03:18

Non-LTR Retrotransposons

As the name suggests, non-LTR retrotransposons lack the long terminal repeats characteristic of the LTR retrotransposons. Additionally, both LTR and non-LTR retrotransposons use distinct mechanisms of mobilization. Non-LTR retrotransposons are further divided into two classes - Long interspersed nuclear elements (LINEs) and short interspersed nuclear elements (SINEs), both of which occur abundantly in most mammals, including humans. Some of the active non-LTR retrotransposons in humans are L1...
13.7K
Cancer-Critical Genes II: Tumor Suppressor Genes01:05

Cancer-Critical Genes II: Tumor Suppressor Genes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
10.0K