Human ALKBH4 interacts with proteins associated with transcription
Linn G Bjørnstad1, Trine J Meza, Marit Otterlei
1Department of Molecular Biosciences, University of Oslo, Oslo, Norway.
Plos One
|November 13, 2012
Summary
Human AlkB homologs ALKBH4 and ALKBH7 have unknown functions. Yeast two-hybrid screens revealed ALKBH4 interacts with chromatin and transcription proteins, suggesting a role in gene regulation or chromatin state.
Area of Science:
- Biochemistry
- Molecular Biology
- Genetics
Background:
- The bacterial AlkB protein repairs DNA/RNA alkyl lesions via direct reversal.
- Human AlkB homologs (ALKBH1-8, FTO) include known demethylases and RNA modification enzymes.
- The functions of ALKBH4 and ALKBH7 remain largely uncharacterized.
Purpose of the Study:
- To investigate the biochemical functions of human ALKBH4 and ALKBH7.
- To identify interaction partners of ALKBH4 and ALKBH7 using yeast two-hybrid screens.
Main Methods:
- Yeast two-hybrid screening to identify protein-protein interactions.
- Analysis of protein interaction domains and subcellular localization.
- Gene expression analysis upon protein over-expression.
Main Results:
- ALKBH4 interacts with chromatin-associated and transcription-related proteins.
- Interaction domains in ALKBH4 partners suggest DNA/chromatin binding.
- Nuclear co-localization observed for some ALKBH4 partners.
- ALKBH4 over-expression had minor effects on global gene expression.
- ALKBH7 over-expression caused larger gene expression changes.
Conclusions:
- ALKBH4 likely plays a role in gene expression regulation or chromatin state.
- Further research is needed to elucidate the precise molecular functions of ALKBH4 and ALKBH7.
Related Concept Videos
02:36RNA Polymerase II Accessory Proteins
Proteins that regulate transcription can do so either via direct contact with RNA Polymerase or through indirect interactions facilitated by adaptors, mediators, histone-modifying proteins, and nucleosome remodelers. Direct interactions to activate transcription is seen in bacteria as well as in some eukaryotic genes. In these cases, upstream activation sequences are adjacent to the promoters, and the activator proteins interact directly with the transcriptional machinery. For example, in...
02:04Co-activators and Co-repressors
Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
02:04Co-activators and Co-repressors
Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
02:16Transcription Factors
Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
02:16Transcription Factors
Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
02:42Eukaryotic Transcription Activators
Transcription activators are proteins that promote the transcription of genes from DNA to RNA. In most cases, these proteins contain two separate domains ‒ a domain that binds to DNA and a domain for activating transcription; however, in some cases, a single domain is responsible for both binding and activation of transcription, as seen in the glucocorticoid receptor and MyoD.
The binding domains are capable of recognizing and interacting with regulatory sequences on the DNA. These domains are...
The binding domains are capable of recognizing and interacting with regulatory sequences on the DNA. These domains are...