scholarly journals EHF is essential for epidermal and colonic epithelial homeostasis, and suppresses Apc-initiated colonic tumorigenesis

Development ◽  
2021 ◽  
Vol 148 (12) ◽  
Author(s):  
Camilla M. Reehorst ◽  
Rebecca Nightingale ◽  
Ian Y. Luk ◽  
Laura Jenkins ◽  
Frank Koentgen ◽  
...  
Keyword(s):  
Dna Binding ◽  
Body Weight Gain ◽  
Binding Domain ◽  
Mouse Strains ◽  
Colonic Epithelium ◽  
Dna Binding Domain ◽  
Corneal Ulcers ◽  
Reduced Body ◽  
Epithelial Homeostasis ◽  
Goblet Cell Differentiation

ABSTRACT Ets homologous factor (EHF) is a member of the epithelial-specific Ets (ESE) family of transcription factors. To investigate its role in development and epithelial homeostasis, we generated a series of novel mouse strains in which the Ets DNA-binding domain of Ehf was deleted in all tissues (Ehf−/−) or specifically in the gut epithelium. Ehf−/− mice were born at the expected Mendelian ratio, but showed reduced body weight gain, and developed a series of pathologies requiring most Ehf−/− mice to reach an ethical endpoint before reaching 1 year of age. These included papillomas in the facial skin, abscesses in the preputial glands (males) or vulvae (females), and corneal ulcers. Ehf−/−mice also displayed increased susceptibility to experimentally induced colitis, which was confirmed in intestinal-specific Ehf knockout mice. Gut-specific Ehf deletion also impaired goblet cell differentiation, induced extensive transcriptional reprogramming in the colonic epithelium and enhanced Apc-initiated adenoma development. The Ets DNA-binding domain of EHF is therefore essential for postnatal homeostasis of the epidermis and colonic epithelium, and its loss promotes colonic tumour development.

scholarly journals EHF is essential for epidermal and colonic epithelial homeostasis and suppresses Apc-initiated colonic tumorigenesis

2021 ◽  
Author(s):  
Camilla M Reehorst ◽  
Rebecca Nightingale ◽  
Ian Y Luk ◽  
Laura Jenkins ◽  
Frank Koentgen ◽  
...  
Keyword(s):  
Dna Binding ◽  
Body Weight Gain ◽  
Sodium Sulphate ◽  
Binding Domain ◽  
Whole Body ◽  
Colonic Epithelium ◽  
Dna Binding Domain ◽  
Corneal Ulcers ◽  
Epithelial Homeostasis ◽  
The Impact

Background: Ets homologous factor (EHF) is a member of the epithelial-specific Ets (ESE) transcription factors. EHF is specifically expressed in epithelial tissues, however its role in development and epithelial homeostasis is largely uncharacterized. Methods: We generated a novel mouse strain in which the Ets DNA binding domain (exon 8) of Ehf was flanked by loxP sites (Ehf Lox/Lox). To inactivate Ehf in the whole body, Ehf Lox/Lox mice were crossed to CMV Cre mice, which were then bred out to generate germline Ehf null (Ehf -/-) mice. To inactivate Ehf specifically in the intestinal epithelium, Ehf Lox/Lox mice were bred to tamoxifen-inducible Villin Cre-ERT2 mice. Ehf Lox/Lox mice were also crossed to tamoxifen-inducible Cdx2 CreERT2;Apc Lox/+ mice to determine the impact of Ehf deletion on Apc-initiated colon cancer development. Results: Transcripts encoding the Ets binding domain of EHF were effectively deleted in all tissues in Ehf -/- mice. Ehf -/- mice were born at the expected Mendelian ratio, but showed reduced body weight gain and developed a series of pathologies during their lifespan that led the majority of Ehf -/- mice to reach an ethical endpoint within one year of age. Most prominent of these were the development of papillomas in the chin, and abscesses in the preputial glands (males) or vulvae (females) which showed evidence of Staphylococcus and Proteus infection. Consistent with the development of papillomas, the epidermis of Ehf -/- mice showed evidence of mild hyperplasia. A subset of Ehf -/- mice also developed cataracts and corneal ulcers. EHF is highly expressed in the colonic epithelium and Ehf -/- mice displayed increased susceptibility to dextran sodium sulphate-induced colitis. This phenotype was confirmed in intestinal-specific Ehf knockout mice, and histopathological analyses revealed reduced numbers of goblet cells and extensive transcriptional reprogramming in the colonic epithelium. Finally, colon-specific deletion of Ehf enhanced Apc-initiated adenoma development, unveiling a novel, tumour suppressive role for EHF in colorectal cancer. Conclusion: The Ets DNA-binding domain of EHF is essential for post-natal homeostasis of the epidermis and colonic epithelium, and functions as a tumour suppressor in the colon.

NMR studies of the R2 repeat and related peptide fragments of the DNA binding domain of c-Myb. New light on the structure and folding of R2.

1999 ◽  
Vol 96 (9/10) ◽  
pp. 1580-1584 ◽  
Author(s):  
I. Ségalas ◽  
S. Desjardins ◽  
H. Oulyadi ◽  
Y. Prigent ◽  
S. Tribouillard ◽  
...  
Keyword(s):  
Dna Binding ◽  
Binding Domain ◽  
Dna Binding Domain ◽  
Peptide Fragments ◽  
Nmr Studies ◽  
Related Peptide

scholarly journals Primary structure of a glycosylated DNA-binding domain in human plasma fibronectin.

1985 ◽  
Vol 260 (4) ◽  
pp. 2301-2306
Author(s):  
H Pande ◽  
J Calaycay ◽  
D Hawke ◽  
C M Ben-Avram ◽  
J E Shively
Keyword(s):  
Dna Binding ◽  
Human Plasma ◽  
Primary Structure ◽  
Binding Domain ◽  
Dna Binding Domain ◽  
Plasma Fibronectin

scholarly journals Functional mechanisms of MYRF DNA-binding domain mutations implicated in birth defects

2021 ◽  
Vol 296 ◽  
pp. 100612
Author(s):  
Chuandong Fan ◽  
Hongjoo An ◽  
Mohamed Sharif ◽  
Dongkyeong Kim ◽  
Yungki Park
Keyword(s):  
Dna Binding ◽  
Birth Defects ◽  
Binding Domain ◽  
Dna Binding Domain ◽  
Functional Mechanisms

scholarly journals Poly(ADP-ribose) synthetase. The DNA binding domain and the automodification domain.

1982 ◽  
Vol 257 (11) ◽  
pp. 6102-6105
Author(s):  
M Nishikimi ◽  
K Ogasawara ◽  
I Kameshita ◽  
T Taniguchi ◽  
Y Shizuta
Keyword(s):  
Dna Binding ◽  
Binding Domain ◽  
Dna Binding Domain

Structural basis of the p53 DNA binding domain and PUMA complex

2021 ◽  
Vol 548 ◽  
pp. 39-46
Author(s):  
Chang Woo Han ◽  
Han Na Lee ◽  
Mi Suk Jeong ◽  
So Young Park ◽  
Se Bok Jang
Keyword(s):  
Dna Binding ◽  
Binding Domain ◽  
Structural Basis ◽  
Dna Binding Domain

The lacI Gene as a Target for Mutation in Transgenic Rodents and Escherichia coli

Genetics ◽  
1998 ◽  
Vol 148 (4) ◽  
pp. 1441-1451
Author(s):  
Johan G de Boer ◽  
Barry W Glickman
Keyword(s):  
Escherichia Coli ◽  
Dna Repair ◽  
Dna Binding ◽  
Transgenic Animals ◽  
Single Copy ◽  
Binding Domain ◽  
Dna Binding Domain ◽  
Large Database ◽  
Deletion Mutations ◽  
Laci Gene

Abstract The lacI gene has been used extensively for the recovery and analysis of mutations in bacteria with various DNA repair backgrounds and after exposure to a wide variety of mutagens. This has resulted in a large database of information on mutational mechanisms and specificity of many mutagens, as well as the effect of DNA repair background on mutagenicity. Most importantly, knowledge about the mutational sensitivity of the lacI gene is now available, yielding information about mutable nucleotides. This popularity and available knowledge resulted in the use of the lacI gene in transgenic rodents for the study of mutagenesis in mammals, where it resides in ~40 repeated copies. As the number of sequenced mutations recovered from these animals increases, we are able to analyze the sites at which mutations have been recovered in great detail and to compare the recovered sites between bacteria and transgenic animals. The nucleotides that code for the DNA-binding domain are nearly saturated with base substitutions. Even after determining the sequences of ~10,000 mutations recovered from the animals, however, new sites and new changes are still being recovered. In addition, we compare the nature of deletion mutations between bacteria and animals. Based on the nature of deletions in the animals, we conclude that each deletion occurs in a single copy of the gene.

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