Related Experiment Video
Updated: May 9, 2026
09:14
Examination of Proteins Bound to Nascent DNA in Mammalian Cells Using BrdU-ChIP-Slot-Western Technique
Published on: January 14, 2016
HDAC3 is essential for DNA replication in hematopoietic progenitor cells
Alyssa R Summers1, Melissa A Fischer, Kristy R Stengel
1Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
The Journal of Clinical Investigation
|August 8, 2013
Summary
Histone deacetylase 3 (HDAC3) is essential for hematopoietic stem cell function and lymphopoiesis. Loss of HDAC3 impairs DNA replication and cell proliferation, leading to compromised stem cell activity and reduced lymphoid cell production.
Area of Science:
- Hematopoiesis
- Molecular Biology
- Cancer Biology
Background:
- Histone deacetylase 3 (HDAC3) plays a role in gene expression and chromatin structure.
- HDAC3 is implicated in leukemia and lymphoma due to its association with oncoproteins.
Purpose of the Study:
- To investigate the physiological roles of Hdac3 in hematopoiesis using a conditional deletion mouse model.
- To understand the impact of Hdac3 deletion on lymphoid cell development and hematopoietic stem cell function.
Main Methods:
- Conditional deletion of Hdac3 in mice using the Vav-Cre transgenic allele.
- Phenotypic and functional analysis of hematopoietic cells, including bone marrow transplantation and in vitro proliferation assays.
- BrdU and DNA fiber labeling to assess DNA replication and cell cycle progression.
Main Results:
- Hdac3 deletion led to a significant loss of lymphoid cells, hypocellular bone marrow, and mild anemia.
- Hdac3 is crucial for the development of early lymphoid progenitor cells but not multipotent progenitors.
- Hdac3-deficient stem cells showed severely compromised competitive bone marrow transplantation potential.
- In vitro, Hdac3(-/-) stem and progenitor cells failed to proliferate and remained undifferentiated.
- Impaired DNA replication and S phase transit were observed in Hdac3-deficient hematopoietic stem and progenitor cells.
Conclusions:
- HDAC3 is essential for the passage of hematopoietic stem/progenitor cells through S phase.
- HDAC3 is required for maintaining hematopoietic stem cell functions and lymphopoiesis.
- Targeting HDAC3 may offer therapeutic strategies for hematological malignancies.
Related Concept Videos
02:38S-Cdk Initiates DNA Replication
The cell cycle is a series of events leading to DNA duplication followed by the division of cell content to form two daughter cells. The cell cycle progresses in four stages—the cell increases in size (gap 1 or G1-phase), duplicates its DNA (synthesis or S-phase), prepares to divide (gap 2 or G2-phase), and divides (mitosis or M-phase).
Two states at the origin of replication
In eukaryotes, the initiation of replication occurs at many sites on the chromosomes, called the origins of replication.
Two states at the origin of replication
In eukaryotes, the initiation of replication occurs at many sites on the chromosomes, called the origins of replication.
02:38S-Cdk Initiates DNA Replication
The cell cycle is a series of events leading to DNA duplication followed by the division of cell content to form two daughter cells. The cell cycle progresses in four stages—the cell increases in size (gap 1 or G1-phase), duplicates its DNA (synthesis or S-phase), prepares to divide (gap 2 or G2-phase), and divides (mitosis or M-phase).
Two states at the origin of replication
In eukaryotes, the initiation of replication occurs at many sites on the chromosomes, called the origins of replication.
Two states at the origin of replication
In eukaryotes, the initiation of replication occurs at many sites on the chromosomes, called the origins of replication.
02:37Restarting Stalled Replication Forks
DNA replication is initiated at sites containing predefined DNA sequences known as origins of replication. DNA is unwound at these sites by the minichromosome maintenance (MCM) helicase and other factors such as Cdc45 and the associated GINS complex.The unwound single strands are protected by replication protein A (RPA) until DNA polymerase starts synthesizing DNA at the 5’ end of the strand in the same direction as the replication fork. To prevent the replication fork from falling apart, a...
02:36DNA Damage can Stall the Cell Cycle
In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
02:36DNA Damage Can Stall the Cell Cycle
In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
02:31Chromosome Replication
Before a cell can divide, it must accurately replicate all of its chromosomes, including the DNA and its associated histone and non-histone proteins. This process begins at numerous origins of replication during the S phase of the cell cycle in each of a cell’s chromosomes simultaneously. Certain nucleotides can act as origins of replication, but these sequences are not well defined - especially in complex, multi-cellular, eukaryotic species. The length of DNA that spans an origin of...