Title

Authors

Affiliation

Department of Biology, Faculty of Mathematics and Natural Sciences, Brawijaya University, Malang, East Java, Indonesia

Email

fatchiya@gmail.com, fatchiya@ub.ac.id; *Corresponding author

Article Type

Hypothesis

Date

Received August 22, 2013; Accepted August 24, 2013; Published August 28, 2013

Erythropoietin (EPO) is a glycoprotein hormone that play a role as key regulator in the production of red blood cells. The promoter region of EPO is methylated in normoxic (non-hypoxia) condition, but not in hypoxic condition. Methylation of the EPO enhancer region decline the transcription activity of EPO gene. The aim of this study is to investigate how different methylation percentage affected on the regulation and transcriptional activity of EPO gene. The DNA sequence of erythropoietin gene and protein sequence was retrieved from the sequence database of NCBI. DNA structure was constructed using 3D-DART web server and modeling structure of HIF1 predicted using SWISS-MODEL web server. Methylated DNA sequence of EPO gene using performed with YASARA View software and docking of EPO gene and transcription factor HIF1 analyzed by using HADDOCK webserver. Our result showed that binding energy in 46% methylated DNA was higher ( 161,45 kcal/mol) than in unmethylated DNA ( 194,16 kcal/mol) and 8% methylated DNA ( 175,94 kcal/mol). So, we presume that a silencing mechanism of the Epo gene by methylation is correlated with the binding energy, which is required for interaction. A higher methylation percentage correlates with a higher binding energy which can cause an unstable interaction between DNA and transcription factor. In conclution, methylation of promoter and enhancer region of Epo gene leads to silencing.

Keywords

EPO, HIF-1, methylation, promoter, transcription.

Citation

Dewi & Fatchiyah,  Bioinformation 9(15): 782-787 (2013)

Edited by

P Kangueane

ISSN

0973-2063

Publisher

Biomedical Informatics

License

This is an Open Access article which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. This is distributed under the terms of the Creative Commons Attribution License.