geoscience.net logo
+ Resolve Article
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter

+ Translate
+ Subscribe to Site Feed
GeoScience Most Shared ContentMost Shared Content

Promiscuous DNA-binding of a mutant zinc finger protein corrupts the transcriptome and diminishes cell viability


, : Promiscuous DNA-binding of a mutant zinc finger protein corrupts the transcriptome and diminishes cell viability. Nucleic Acids Research (): -

NlmCategory="UNASSIGNED">The rules of engagement between zinc finger transcription factors and DNA have been partly defined by in vitro DNA-binding and structural studies, but less is known about how these rules apply in vivo Here, we demonstrate how a missense mutation in the second zinc finger of Krüppel-like factor-1 (KLF1) leads to degenerate DNA-binding specificity in vivo, resulting in ectopic transcription and anemia in the Nan mouse model. We employed ChIP-seq and 4sU-RNA-seq to identify aberrant DNA-binding events genome wide and ectopic transcriptional consequences of this binding. We confirmed novel sequence specificity of the mutant recombinant zinc finger domain by performing biophysical measurements of in vitro DNA-binding affinity. Together, these results shed new light on the mechanisms by which missense mutations in DNA-binding domains of transcription factors can lead to autosomal dominant diseases.

US$19.90

PMID: 27899603

DOI: 10.1093/nar/gkw1014


Other references

Fazzi E.; Lanzi G.; Gerardo A.; Ometto A.; Rondini G., 1991: Correlation between clinical and ultrasound findings in preterm infants with cystic periventricular leukomalacia. Cystic periventricular Leukomalacia (CPVL), a hypoxic-ischemic lesion of the neonatal brain, which cna now be diagnosed in life thanks to ultrasound brain scanning, is considered to be one of the main causes of cerebral palsy (CP), especially in p...

Carter Thompson, R.; Kennedy, K., 2000: Addressing a need for youth programs. The City of Charlottetown Parks and Recreation Department's Adventure Group (Canada) is profiled. The goals of this programme are to offer at-risk youth the chance to participate in activities that require them to develop team skills such as...

Anonymous, 1972: Anxiety of patients in research. British Medical Journal 4(5841): 624-624

Wang, E.T.; de Koning, L.; Kanaya, A.M., 2010: Higher protein intake is associated with diabetes risk in South Asian Indians: the Metabolic Syndrome and Atherosclerosis in South Asians Living in America (MASALA) study. Despite a high prevalence of type 2 diabetes in South Asian Indians, the impact of diet in this high-risk ethnic group has not been fully explored. The association of macronutrient intake and diabetes in South Asian Indians was examined in this cr...

van de Vijver, D.A.M.C.; Boucher, C.A.B., 2011: The risk of HIV drug resistance following implementation of pre-exposure prophylaxis. Results of trials determining if pre-exposure prophylaxis (PrEP) with antiretroviral drugs prevents transmission of HIV are expected soon. Tenofovir and emtricitabine--currently evaluated as PrEP--are popular in treatment of HIV. Drug resistance c...

Horning E.C.; Carroll D.I.; Nowlin J.G.; Stillwell R.N., 1982: Detection limits in trace organic analysis with bio analytical systems based on mass spectrometry. Abstracts of Papers American Chemical Society 183: CHED-25

Teramachi, H., 2016: Pharmacy Education and the Role of the Local Pharmacy at Gifu Pharmaceutical University Pharmacy. Gifu Pharmaceutical University Pharmacy was established in front of Gifu University Hospital (GUH) as a pharmacy attached to the university, the first in Japan in 1998. When GUH moved in 2004, Gifu Pharmaceutical University Pharmacy was built in i...

Iliceto, S.; Amico, A.; Tota, F.; D'Ambrosio, G., 1987: Doppler echocardiography. II. Cardiologia 32(12): 1547-1557

Goldman, M.P.; Weiss, R.A.; Weiss, M.A., 2005: Intense pulsed light as a nonablative approach to photoaging. To describe the introduction and use of intense pulsed light (IPL) to treat vascular and pigmented lesions comprising photorejuvenation and its use in photodynamic therapy. Review of the medical literature and the authors' experience with IPL...

Costa, A.; Rovati, C.; Degetto, P.; Midiri, R.; Valli, A.; L.D.co, C.; Arw, K.; Frizzi, R.; Niccolini, A.; Andreotti, C.; Comotti, C., 1981: Effects of dietetic integration with essential amino acids in uremic patients treated with long-term hemodialysis. Minerva Dietologica E Gastroenterologica 27(1): 141-145