Sunday, February 8, 2009


Overexpression of Lef1 diminishes the effects of Beta-Catenin on Notch1.  Lef1 is more strongly expressed in growth plate cartilage than articular cartilage.

Looping Mediated Interaction between the Promoter and 3′ UTR Regulates Type II Collagen Expression in Chondrocytes

"Type II collagen is the major component of articular cartilage and is mainly synthesized by chondrocytes. Repeated sub-culturing of primary chondrocytes leads to reduction of type II collagen gene (Col2a1) expression, which mimics the process of chondrocyte dedifferentiation. We have investigated the crosstalk between cis-acting DNA element and transcription factor on Col2a1 expression in primary chondrocytes. Bioinformatic analysis revealed the potential regulatory regions in the Col2a1 genomic locus. Among them, promoter and 3′ untranslated region (UTR) showed highly accessible chromatin architecture with enriched recruitment of active chromatin markers in primary chondrocytes. 3′ UTR has a potent enhancer function which recruits Lef1 (Lymphoid enhancer binding factor 1) transcription factor, leading to juxtaposition of the 3′ UTR with the promoter through gene looping resulting in up-regulation of Col2a1 gene transcription. Knock-down of endogenous Lef1 level significantly reduced the gene looping and subsequently down-regulated Col2a1 expression. However, these regulatory loci become inaccessible due to condensed chromatin architecture as chondrocytes dedifferentiate which was accompanied by a reduction of gene looping and down-regulation of Col2a1 expression. Lef1 mediated looping between promoter and 3′ UTR under the permissive chromatin architecture upregulates Col2a1 expression in primary chondrocytes."

"Lef1 over-expression significantly increased Col2a1 expression"

"Expression of TCF-3, TCF-4 and Lef1 have been reported in the cartilage. Upregulated TCF-1 expression is confined to the prehypertrophic chondrocytes and in the surrounding perichondrium. TCF-3 can be detected in the whole cartilage, while hypertrophic chondrocytes in Col2a1-ICAT transgenic mice only express TCF-4"

" β-catenin is essential for the early stages of cartilage growth and development whereas over-expression of β-catenin in the adult cartilage is accompanied by cartilage destruction. Inhibition of β-catenin signaling in chondrocytes resulted in significant reduction of expression of Lef/TCF family members such as Lef1, TCF-3 and TCF-4 and showed defects in post-natal cartilage development and delayed chondrogenesis which is accompanied by significant decrease in the cartilage marker gene Col2a1"

"Absence of Lef1 leads to increased apoptosis of chondrocytes and similar effect is also found upon Col2a1 deficiency. Lef1 suppressed cells reduced expression of Col11a1{up}"

"Col11a1, a heterotrimer of alpha 1 (XI) collagen (Col11a1), alpha 2 (XI) collagen (Col11a2) and alpha 1 (II) collagen, is mainly expressed in the articular cartilage and vitreous fluid of the eye, and is responsible for the proper type II collagen fibril formation"

"Mutation of Type XI{up} collagen resulted in accumulation of degraded type II collagen in articular cartilage"

Since LSJL gene expression was taken at 1 hour after last loading, it's possible that Lef1 was upregulated sooner than that and the residual effects are taken at one hour.

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