AI Article Synopsis
Article Abstract
The SP1/Krüppel-like Factor (SP1/KLF) family of transcription factors plays a role in diverse cellular processes, including proliferation, differentiation and control of gene transcription. The discovery of KLF1 (EKLF), a key regulator of HBB (β-globin) gene expression, expanded our understanding of the role of KLFs in erythropoiesis. In this study, we investigated a mechanism of HBG (γ-globin) regulation by KLF4. siRNA-mediated gene silencing and enforced expression of KLF4 in K562 cells substantiated the ability of KLF4 to positively regulate endogenous HBG gene transcription. The physiological significance of this finding was confirmed in primary erythroid cells, where KLF4 knockdown at day 11 significantly attenuated HBG mRNA levels and enforced expression at day 28 stimulated the silenced HBG genes. In vitro binding characterization using the γ-CACCC and β-CACCC probes demonstrated KLF4 preferentially binds the endogenous γ-CACCC, while CREB binding protein (CREBBP) binding was not selective. Co-immunoprecipitation studies confirmed protein-protein interaction between KLF4 and CREBBP. Furthermore, sequential chromatin immunoprecipitation assays showed co-localization of both factors in the γ-CACCC region. Subsequent luciferase reporter studies demonstrated that KLF4 trans-activated HBG promoter activity and that CREBBP enforced expression resulted in gene repression. Our data supports a model of antagonistic interaction of KLF4/CREBBP trans-factors in HBG regulation.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4288826 | PMC |
| http://dx.doi.org/10.1111/j.1365-2141.2011.08710.x | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Understanding stakeholder responses to the electronic cigarette flavor ban in China: A news media analysis.
Public Health
December 2024
School of Public Health, Peking University, Beijing, China; China Center for Health Development Studies, Peking University, Beijing, China. Electronic address:
Objectives: Electronic cigarettes (e-cigarettes) have been attracting users around the world due in part to appealing flavors. Many countries and regions have now taken action to limit the sales of flavored e-cigarettes. In 2022, China implemented a flavor ban on e-cigarettes, prohibiting all but tobacco-flavor.
View Article and Find Full Text PDFBioactivity Profiling of Chemical Mixtures for Hazard Characterization.
Environ Sci Technol
December 2024
Centre for Environmental Research and Justice (CERJ), School of Biosciences, The University of Birmingham, Birmingham B15 2TT, U.K.
The assessment and regulation of chemical toxicity to protect human health and the environment are done one chemical at a time and seldom at environmentally relevant concentrations. However, chemicals are found in the environment as mixtures, and their toxicity is largely unknown. Understanding the hazard posed by chemicals within the mixture is critical to enforce protective measures.
View Article and Find Full Text PDFMiR-495 reverses in the mechanical unloading, random rotating and aging induced muscle atrophy via targeting MyoD and inactivating the Myostatin/TGF-β/Smad3 axis.
Arch Biochem Biophys
December 2024
Institute for Special Environmental Biophysics, Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, 710072, Shaanxi, China. Electronic address:
Mechanical unloading can lead to homeostasis imbalance and severe muscle disease, in which muscle atrophy was one of the disused diseases. However, there were limited therapeutic targets for such diseases. In this study, miR-495 was found dramatically reduced in atrophic skeletal muscle induced by mechanical unloading models both in vitro and in vivo, including the random positioning model (RPM), tail-suspension (TS) model, and aged mice model.
View Article and Find Full Text PDFThe effects of message framing on US police chiefs' support for interventions for opioid use disorder: a randomized survey experiment.
Health Justice
December 2024
University of Central Florida College of Community Education and Innovation, Orlando, FL, United States.
Background: US chiefs of police hold significant influence over the perceived acceptability and appropriateness of interventions for opioid use disorder (OUD) among the public, elected officials, and subordinate officers. This study assessed whether police chiefs' support for such interventions was sensitive to framing an intervention's benefits in terms that emphasize public health and harm reduction outcomes, versus terms typically indicative of public safety outcomes.
Methods: A two-armed survey utilizing a randomized, between-subjects design tested framing-based variance in support among US chiefs of police for overdose prevention centers, syringe service programs (SSPs), Good Samaritan laws, police naloxone distribution, trustworthiness of officers in recovery from OUD, and related propositions.
Setting of residue definitions and toxicological reference values for ethiprole.
EFSA J
December 2024
In accordance with Article 6 of Regulation (EC) No 396/2005, the original evaluating Member State (EMS), the United Kingdom, received an application from Bayer CropScience to set an import tolerance for the non-approved active substance ethiprole in rice. In the framework of the assessment process, the application was re-allocated to the Netherlands and the purpose of the application was changed to only set European residue definitions and toxicological reference values for the active substance ethiprole. Based on the assessment of the available toxicological data, an acceptable daily intake of 0.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!