scholarly journals The transcription factor Znf219 regulates chondrocyte differentiation by assembling a transcription factory with Sox9

2010 ◽  
Vol 123 (21) ◽  
pp. 3780-3788 ◽  
Author(s):  
Y. Takigawa ◽  
K. Hata ◽  
S. Muramatsu ◽  
K. Amano ◽  
K. Ono ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Chondrocyte Differentiation ◽  
Transcription Factory

scholarly journals L-Sox5 and Sox6 Drive Expression of the Aggrecan Gene in Cartilage by Securing Binding of Sox9 to a Far-Upstream Enhancer

2008 ◽  
Vol 28 (16) ◽  
pp. 4999-5013 ◽  
Author(s):  
Yu Han ◽  
Véronique Lefebvre
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Transgenic Mice ◽  
Mode Of Action ◽  
High Mobility ◽  
Recognition Site ◽  
High Mobility Group ◽  
Minimal Promoter ◽  
Chondrocyte Differentiation ◽  
Cartilage Proteoglycan

ABSTRACT The Sry-related high-mobility-group box transcription factor Sox9 recruits the redundant L-Sox5 and Sox6 proteins to effect chondrogenesis, but the mode of action of the trio remains unclear. We identify here a highly conserved 359-bp sequence 10 kb upstream of the Agc1 gene for aggrecan, a most essential cartilage proteoglycan and key marker of chondrocyte differentiation. This sequence directs expression of a minimal promoter in both embryonic and adult cartilage in transgenic mice, in a manner that matches Agc1 expression. The chondrogenic trio is required and sufficient to mediate the activity of this enhancer. It acts directly, Sox9 binding to a critical cis-acting element and L-Sox5/Sox6 binding to three additional elements, which are cooperatively needed. Upon binding to their specific sites, L-Sox5/Sox6 increases the efficiency of Sox9 binding to its own recognition site and thereby robustly potentiates the ability of Sox9 to activate the enhancer. L-Sox5/Sox6 similarly secures Sox9 binding to Col2a1 (encoding collagen-2) and other cartilage-specific enhancers. This study thus uncovers critical cis-acting elements and transcription factors driving Agc1 expression in cartilage and increases understanding of the mode of action of the chondrogenic Sox trio.

scholarly journals Basic Helix-loop-helix Protein DEC1 Promotes Chondrocyte Differentiation at the Early and Terminal Stages

2002 ◽  
Vol 277 (51) ◽  
pp. 50112-50120 ◽  
Author(s):  
Ming Shen ◽  
Eri Yoshida ◽  
Weiqun Yan ◽  
Takeshi Kawamoto ◽  
Ketut Suardita ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Growth Plate ◽  
Chondrogenic Differentiation ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Indian Hedgehog ◽  
Chondrocyte Differentiation ◽  
Growth Plate Chondrocytes ◽  
Basic Helix Loop Helix ◽  
Helix Loop Helix

The mRNA level of basic helix-loop-helix transcription factor DEC1 (BHLHB2)/Stra13/Sharp2 was up-regulated during chondrocyte differentiation in cultures of ATDC5 cells and growth plate chondrocytes, and in growth plate cartilagein vivo. Forced expression of DEC1 in ATDC5 cells induced chondrogenic differentiation, and insulin increased this effect of DEC1 overexpression. Parathyroid hormone (PTH) and PTH-related peptide (PTHrP) suppressed DEC1 expression and the differentiation of ATDC5 cells, but DEC1 overexpression antagonized this inhibitory action of PTH/PTHrP. Transforming growth factor-β or bone morphogenetic protein-2, as well as insulin, induced DEC1 expression in ATDC5 cultures where it induced chondrogenic differentiation. In pellet cultures of bone marrow mesenchymal stem cells exposed to transforming growth factor-β and insulin, DEC1 was induced at the earliest stage of chondrocyte differentiation and also at the hypertrophic stage. Overexpression of DEC1 in the mesenchymal cells induced the mRNA expressions of type II collagen, Indian hedgehog, and Runx2, as well as cartilage matrix accumulation; overexpression of DEC1 in growth plate chondrocytes at the prehypertrophic stage increased the mRNA levels of Indian hedgehog, Runx2, and type X collagen, and also increased alkaline phosphatase activity and mineralization. To our knowledge, DEC1 is the first transcription factor that can promote both chondrogenic differentiation and terminal differentiation.

A transcription factor Znf219 regulates chondrogenesis by forming a transcription factory complex with Sox9

Bone ◽  
2009 ◽  
Vol 44 ◽  
pp. S43
Author(s):  
Y. Takigawa ◽  
K. Hata ◽  
S. Muramatsu ◽  
K. Amano ◽  
K. Ono ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Transcription Factory

scholarly journals Dmrt2 promotes transition of endochondral bone formation by linking Sox9 and Runx2

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Koichiro Ono ◽  
Kenji Hata ◽  
Eriko Nakamura ◽  
Shota Ishihara ◽  
Sachi Kobayashi ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Bone Formation ◽  
Skeletal Development ◽  
Endochondral Bone Formation ◽  
Chondrocyte Differentiation ◽  
Endochondral Bone ◽  
Chondrocyte Hypertrophy ◽  
Hypertrophic Chondrocyte ◽  
Delayed Initiation ◽  
Related Transcription Factor

AbstractEndochondral bone formation is fundamental for skeletal development. During this process, chondrocytes undergo multiple steps of differentiation and coordinated transition from a proliferating to a hypertrophic stage, which is critical to advance skeletal development. Here, we identified the transcription factor Dmrt2 (double-sex and mab-3 related transcription factor 2) as a Sox9-inducible gene that promotes chondrocyte hypertrophy in pre-hypertrophic chondrocytes. Epigenetic analysis further demonstrated that Sox9 regulates Dmrt2 expression through an active enhancer located 18 kb upstream of the Dmrt2 gene and that this enhancer’s chromatin status is progressively activated through chondrocyte differentiation. Dmrt2-knockout mice exhibited a dwarf phenotype with delayed initiation of chondrocyte hypertrophy. Dmrt2 augmented hypertrophic chondrocyte gene expression including Ihh through physical and functional interaction with Runx2. Furthermore, Dmrt2 deficiency reduced Runx2-dependent Ihh expression. Our findings suggest that Dmrt2 is critical for sequential chondrocyte differentiation during endochondral bone formation and coordinates the transcriptional network between Sox9 and Runx2.

Transcription factor/DNA interactions visualized by electron spectroscopic imaging

1992 ◽  
Vol 50 (1) ◽  
pp. 450-451
Author(s):  
David P. Bazett-Jones ◽  
Mark L. Brown
Keyword(s):  
Transcription Factor ◽  
Dna Sequences ◽  
Transcription Initiation ◽  
Molecular Mechanisms ◽  
Phosphorus Content ◽  
Spectroscopic Imaging ◽  
Electron Spectroscopic Imaging ◽  
Dna Backbone ◽  
Two Parameters ◽  
High Level

A multisubunit RNA polymerase enzyme is ultimately responsible for transcription initiation and elongation of RNA, but recognition of the proper start site by the enzyme is regulated by general, temporal and gene-specific trans-factors interacting at promoter and enhancer DNA sequences. To understand the molecular mechanisms which precisely regulate the transcription initiation event, it is crucial to elucidate the structure of the transcription factor/DNA complexes involved. Electron spectroscopic imaging (ESI) provides the opportunity to visualize individual DNA molecules. Enhancement of DNA contrast with ESI is accomplished by imaging with electrons that have interacted with inner shell electrons of phosphorus in the DNA backbone. Phosphorus detection at this intermediately high level of resolution (≈lnm) permits selective imaging of the DNA, to determine whether the protein factors compact, bend or wrap the DNA. Simultaneously, mass analysis and phosphorus content can be measured quantitatively, using adjacent DNA or tobacco mosaic virus (TMV) as mass and phosphorus standards. These two parameters provide stoichiometric information relating the ratios of protein:DNA content.

The role of transcription factor Egr‐1 in IL‐1 up‐regulation of tubular CD44 expression

Nephrology ◽  
2000 ◽  
Vol 5 (3) ◽  
pp. A92-A92
Author(s):  
Takazoe K ◽  
Foti R ◽  
Hurst La ◽  
Atkins Rc ◽  
Nikolic‐Paterson DJ.
Keyword(s):  
Transcription Factor ◽  
Cd44 Expression
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