Related Experiment Video
Updated: Jul 6, 2025
09:23
Efficient Differentiation of Pluripotent Stem Cells to NKX6-1+ Pancreatic Progenitors
Published on: March 7, 2017
8.0K
PRDM3/16 Regulate Chromatin Accessibility Required for NKX2-1 Mediated Alveolar Epithelial Differentiation and
Hua He1,2, Sheila M Bell3, Ashley Kuenzi Davis3
1Key Laboratory of Birth Defects and Related Disease of Women and Children of MOE, West China Second University Hospital Sichuan University, Chengdu, Sichuan, 610041, China.
Biorxiv : the Preprint Server for Biology
|January 8, 2024
Summary
PRDM3 and PRDM16 regulate lung development by controlling chromatin accessibility at key developmental genes. Their absence leads to respiratory failure and altered alveolar cell differentiation.
Area of Science:
- Developmental Biology
- Epigenetics
- Pulmonary Medicine
Background:
- Lung morphogenesis and epithelial cell differentiation are controlled by transcriptional regulators like NKX2-1.
- Mechanisms linking chromatin accessibility, epigenetic changes, and NKX2-1 co-activator interactions in alveolar cell differentiation remain unclear.
Approach:
- Investigated the roles of PRDM3 and PRDM16 in lung development using genetic deletion models in mice.
- Employed single-cell RNA-seq, ATAC-seq, and CUT&RUN to analyze chromatin accessibility and gene regulation.
- Performed network analysis to identify PRDM3/16-regulated genes crucial for alveolar cell function.
Key Points:
- Combined deletion of Prdm3 and Prdm16 in lung endoderm caused perinatal lethality and loss of AT2 cells, with accumulation of AT1 cells.
- PRDM3 and PRDM16 enhance chromatin accessibility at NKX2-1 targets, binding with NKX2-1 at cis-regulatory elements.
- PRDM3/16 regulate genes essential for perinatal AT2 cell differentiation, surfactant homeostasis, and innate immunity.
Conclusions:
- PRDM3 and PRDM16 are critical for regulating chromatin accessibility and mediating cell differentiation decisions during lung morphogenesis.
- NKX2-1-dependent alveolar epithelial cell differentiation is epigenomically controlled by PRDM3/16.
More Related Videos
Related Concept Videos
02:23Master Transcription Regulators
6.9K
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...
6.9K
02:41Chromatin Structure Regulates pre-mRNA Processing
7.0K
In eukaryotic cells, nascent mRNA transcripts need to undergo many post-transcriptional modifications to reach the cell cytoplasm and translate into functional proteins. For a long time, transcription and pre-mRNA processing were considered two independent events that occur sequentially in the cell. However, it has now been well established that transcription and pre-mRNA processing are two simultaneous processes that are precisely regulated inside the cell.
The chromatin structure, especially...
The chromatin structure, especially...
7.0K
02:36RNA Polymerase II Accessory Proteins
9.2K
Proteins that regulate transcription can do so either via direct contact with RNA Polymerase or through indirect interactions facilitated by adaptors, mediators, histone-modifying proteins, and nucleosome remodelers. Direct interactions to activate transcription is seen in bacteria as well as in some eukaryotic genes. In these cases, upstream activation sequences are adjacent to the promoters, and the activator proteins interact directly with the transcriptional machinery. For example, in...
9.2K
01:32Chromatin Modification in iPS Cells
1.7K
Chromatin modification alters gene expression; therefore, scientists can add histone-modifying enzymes, histone variants, and chromatin remodeling complexes to somatic cells to aid reprogramming into pluripotent stem (iPS) cells.
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
1.7K
01:24Methods of Nuclear Reprogramming
1.8K
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...
1.8K
02:35Chromatin Position Affects Gene Expression
23.3K
Chromatin is the massive complex of DNA and proteins packaged inside the nucleus. The complexity of chromatin folding and how it is packaged inside the nucleus greatly influences access to genetic information. Generally, the nucleus' periphery is considered transcriptionally repressive, while the cell's interior is considered a transcriptionally active area.
Topologically Associated Domains (TADs)
The 3-dimensional positioning of chromatin in the nucleus influences the...
Topologically Associated Domains (TADs)
The 3-dimensional positioning of chromatin in the nucleus influences the...
23.3K