alexa Long-range regulation of alpha globin gene expression during erythropoiesis.
Genetics & Molecular Biology

Genetics & Molecular Biology

Journal of Molecular Biomarkers & Diagnosis

Author(s): Higgs DR, Wood WG

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Abstract PURPOSE OF REVIEW: The analysis of globin gene expression during erythropoiesis has established many principles underlying normal mammalian gene expression. New aspects of gene regulation have been revealed by natural mutations that downregulate globin gene expression and cause thalassemia. Deletions involving sequences upstream of the alpha and beta clusters suggested that the globin genes might be controlled by remote regulatory elements. This was demonstrated experimentally and suggested that many mammalian genes may be controlled in a similar manner. RECENT FINDINGS: Completion of the Human Genome Project and the associated encyclopaedia of DNA elements (ENCODE) project confirmed that human gene expression is commonly controlled by long-range, cis-acting elements. The development of chromatin immunoprecipitation has allowed us to identify binding of transcription factors and chromatin modifications at the key cis-acting sequences in vivo. In addition, chromosome conformation capture has enabled us to address the topological models proposed to mediate long-range interactions. Together, these methods have given us some insight into how long-range elements may influence gene expression and how this process may be subverted in thalassemia. SUMMARY: The review asks how remote elements regulate alpha globin expression and how natural mutations interfere with this mechanism to cause alpha thalassemia. We also speculate as to why long-range control of gene expression may have evolved in higher organisms. This article was published in Curr Opin Hematol and referenced in Journal of Molecular Biomarkers & Diagnosis

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