Related Experiment Video

Updated: Jul 14, 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

Haploinsufficient prostate tumor suppression by Nkx3.1: a role for chromatin accessibility in dosage-sensitive gene

Ashish P Mogal1, Riet van der Meer, Philip S Crooke

  • 1Department of Pathology, Vanderbilt University Medical Center, Nashville 37232, USA.

The Journal of Biological Chemistry
|July 3, 2007
PubMed

Insights

Loss of one Nkx3.1 gene copy (haploinsufficiency) affects prostate tumor initiation. Reactivating gene expression via histone acetylation can restore Nkx3.1 function and suppress tumors.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Epigenetics

Background:

  • Transcription factor haploinsufficiency contributes to disease pathogenesis, including cancer.
  • Nkx3.1 (a tumor suppressor) haploinsufficiency in mice leads to stochastic inactivation of dosage-sensitive target genes during prostate tumor initiation.

Purpose of the Study:

  • To investigate the role of histone acetylation in Nkx3.1 dosage sensitivity.
  • To elucidate the mechanism by which Nkx3.1 regulates target gene expression and its impact on prostate tumorigenesis.

Main Methods:

  • Utilizing a mouse model of prostate tumor initiation.
  • Employing the histone deacetylase inhibitor Trichostatin A to modulate histone acetylation.
  • Developing a mathematical model to describe Nkx3.1-histone acetyltransferase association.
  • Performing chromatin immunoprecipitation assays to identify protein interactions.
  • Assessing the function of the intelectin/omentin gene in tumor suppression.

Main Results:

  • Dosage sensitivity of Nkx3.1 target genes correlates with differential histone H3/H4 acetylation states.
  • Histone acetylation induction reactivates Nkx3.1 binding and expression of dosage-sensitive genes.
  • Nkx3.1 associates with and recruits the histone acetyltransferase p300/CREB-binding protein-associated factor (PCAF) to chromatin.
  • The intelectin/omentin gene, a dosage-sensitive target, suppresses prostate tumorigenicity.

Conclusions:

  • The interplay between transcription factor dosage and chromatin modification (histone acetylation) is crucial for regulating target gene expression in prostate tumor initiation.
  • Targeting epigenetic mechanisms, such as histone acetylation, offers potential therapeutic strategies for Nkx3.1-related cancers.

More Related Videos

Efficient Differentiation of Pluripotent Stem Cells to NKX6-1+ Pancreatic Progenitors09:23

Efficient Differentiation of Pluripotent Stem Cells to NKX6-1+ Pancreatic Progenitors

Published on: March 7, 2017

HOX Loci Focused CRISPR/sgRNA Library Screening Identifying Critical CTCF Boundaries10:10

HOX Loci Focused CRISPR/sgRNA Library Screening Identifying Critical CTCF Boundaries

Published on: March 31, 2019

Related Concept Videos

Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
Inheritance of Chromatin Structures03:17

Inheritance of Chromatin Structures

Epigenetics is the study of inherited changes in a cell's phenotype without changing the DNA sequences. It provides a form of memory for the differential gene expression pattern to maintain cell lineage, position-effect variegation, dosage compensation, and maintenance of chromatin structures such as telomeres and centromeres. For example, the structure and location of the centromere on chromosomes are epigenetically inherited. Its functionality is not dictated or ensured by the underlying DNA...
Loss of Tumor Suppressor Gene Functions01:12

Loss of Tumor Suppressor Gene Functions

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
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...
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.
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...