Related Experiment Video
Updated: May 20, 2026
08:19
Evaluation of Keratinocyte Proliferation on Two- and Three-dimensional Type I Collagen Substrates
Published on: April 22, 2019
Looping mediated interaction between the promoter and 3' UTR regulates type II collagen expression in chondrocytes
Arijita Jash1, Kangsun Yun, Anupama Sahoo
1School of Life Sciences and Immune Synapse Research Center, Gwangju Institute of Science and Technology (GIST), Gwangju, Korea.
Plos One
|July 21, 2012
Summary
Lymphoid enhancer binding factor 1 (Lef1) facilitates gene looping between the promoter and 3' untranslated region (UTR) to upregulate type II collagen (Col2a1) expression in chondrocytes. This process is disrupted during chondrocyte dedifferentiation due to chromatin changes.
Area of Science:
- Molecular Biology
- Cell Biology
- Genetics
Background:
- Type II collagen (Col2a1) is crucial for articular cartilage function.
- Chondrocyte dedifferentiation, induced by sub-culturing, reduces Col2a1 expression.
- Mechanisms regulating Col2a1 transcription during dedifferentiation remain unclear.
Purpose of the Study:
- Investigate the transcriptional regulation of Col2a1 during chondrocyte dedifferentiation.
- Identify cis-acting DNA elements and transcription factors involved in Col2a1 regulation.
- Elucidate the role of gene looping in Col2a1 expression.
Main Methods:
- Bioinformatic analysis of the Col2a1 genomic locus.
- Chromatin accessibility assays and active chromatin marker analysis.
- ChIP-qPCR and gene knockdown experiments to assess transcription factor recruitment and function.
Main Results:
- The promoter and 3' UTR of Col2a1 exhibit accessible chromatin in primary chondrocytes.
- Lymphoid enhancer binding factor 1 (Lef1) binds to the 3' UTR, promoting enhancer function.
- Lef1-mediated gene looping between the 3' UTR and promoter upregulates Col2a1 expression.
- Dedifferentiation leads to condensed chromatin, reduced looping, and decreased Col2a1 expression.
Conclusions:
- Lef1-mediated promoter-3' UTR looping is essential for maintaining Col2a1 expression in chondrocytes.
- Chromatin architecture changes during dedifferentiation impair Lef1 function and Col2a1 transcription.
- Understanding these regulatory mechanisms is key for cartilage research.
Related Concept Videos
01:11Fibril-associated Collagen
Fibril-associated collagens are a type of collagens present in the extracellular matrix with interrupted triple helices or FACIT (Fibril-associated collagens interrupted triple-helices). FACIT help connect and attach the collagen fibrils with each other as well as with other proteins of the extracellular matrix.
For example, the type II collagen fibrils in cartilage have covalently bound type IX fibril-associated collagens at regular intervals. Other types of fibril-associated collagens are...
For example, the type II collagen fibrils in cartilage have covalently bound type IX fibril-associated collagens at regular intervals. Other types of fibril-associated collagens are...
01:16TGF - β Signaling Pathway
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...
02:41Chromatin Structure Regulates pre-mRNA Processing
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...
01:05Type IV Collagen of Basal Lamina
Type IV collagen is a 400 nm long, network-forming collagen that acts as a barrier between the epithelial and endothelial cells. Type IV collagen forms the backbone of the basement membrane by scaffolding with laminin, entactin, proteoglycans, and fibronectin. Apart from rendering structural support to the basement membrane, it also helps entail signaling potentials necessary for both pathological and physiological functions.
A type IV collagen molecule has six alpha chains which can exist in...
A type IV collagen molecule has six alpha chains which can exist in...
02:23Master Transcription Regulators
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...
02:36RNA Polymerase II Accessory Proteins
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...