The Transcription Factor ZNF683/HOBIT Regulates Human NK-Cell Development
Mirte Post1, Angelica Cuapio1, Markus Osl1
1Institute of Vascular Biology and Thrombosis Research, Center of Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria.
Frontiers in Immunology
|May 31, 2017
Summary
ZNF683/HOBIT is crucial for human natural killer (NK) cell development from progenitor cells. Knockdown impairs NK cell generation and may increase IFN-γ production in mature NK cells.
Area of Science:
- Immunology
- Molecular Biology
- Cell Biology
Background:
- Natural Killer (NK) cells are critical immune cells.
- Understanding NK cell differentiation is vital for immunotherapy and disease treatment.
Purpose of the Study:
- To investigate the role of transcription factor ZNF683/HOBIT in human NK cell differentiation.
- To elucidate the molecular mechanisms regulating NK cell development.
Main Methods:
- Ex vivo differentiation of human CD34+ cord blood progenitor cells.
- ZNF683/HOBIT gene expression analysis via mRNA quantification.
- shRNA-mediated knockdown of ZNF683/HOBIT.
- Flow cytometry analysis of NK cell populations and receptor expression (NKG2A, KIR).
- Functional assays including degranulation and Interferon-gamma (IFN-γ) production measurement.
Main Results:
- ZNF683/HOBIT is highly upregulated during NK cell differentiation and preferentially expressed in NK cells.
- Knockdown of ZNF683/HOBIT significantly inhibited the generation of CD56+ NK cells from progenitors.
- Mature NK cells from knockdown cultures showed normal NKG2A and KIR receptor levels but an increased proportion of IFN-γ-producing cells.
Conclusions:
- ZNF683/HOBIT plays a key role in human NK cell lineage differentiation.
- ZNF683/HOBIT may negatively regulate IFN-γ production in mature human NK cells.
Related Concept Videos
02:26NF-κB-dependent Signaling Pathway
10.2K
The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
NF-κB-dependent Signaling Mechanism
The...
10.2K
01:30General Transcription Factors
7.3K
Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
7.3K
01:24Methods of Nuclear Reprogramming
2.2K
Nuclear reprogramming is a process of transforming one cell type into an unrelated cell type by epigenetic changes that alter the cell’s original gene expression pattern. Such epigenetic changes force cells to express a different set of genes, which play a significant role in inducing transformation into other cell types. Nuclear reprogramming offers applications in reproductive cloning for livestock propagation and regenerative medicine — developing patient-specific cells for...
2.2K
02:16Transcription Factors
83.2K
Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
83.2K
02:23Master Transcription Regulators
7.9K
Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
7.9K
02:04Co-activators and Co-repressors
8.7K
Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
8.7K