1. A Conserved Regulatory Element in the Mammalian β-Globin Promoters
- Author
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Yoshiaki Onishi, Yuko Wada-Kiyama, Ryoiti Kiyama, and Megumi Kato
- Subjects
Immunology ,Promoter ,Cell Biology ,Hematology ,Biology ,Biochemistry ,Chromatin ,Cell biology ,DNA binding site ,chemistry.chemical_compound ,Histone ,chemistry ,biology.protein ,Nucleosome ,Gene ,Transcription factor ,DNA - Abstract
Recent progresses in the study of histone modifications in gene networks and signaling revived the importance of chromatin for controlling gene functions. However, the difficulty of chromatin study lies first in the number of necleosomes in a cell: roughly 107 nucleosomes, each containing a different DNA sequence, are continuously tied as ”beads and strings”, interacting each other, between the neighboring ones as well as the distant ones. Chromatin organization and nucleosome stability is crucial in massive changes of chromatin enviroment such as in DNA replication and formation of chromosomes at cell division as well as in the local changes as observed in transcription of genes, changes of active/inactive chromatin regions and their boundary formation. One of the best ways to study this complex state is first to classify these nucleosomes based on some definitive criteria. Realization that all nucleosomes are not behaving identically is not new. However, explanation at the molecular level of such differences needs a comprehensive analysis of the genome structure by molecular biological experiments and by computational extractions which became available only in recent years. We provide here evidence for a conserved regulatory element for transcription of the β-like globin gene as a summary of our recent studies of a total of over 30 genes using experimental and/or computational approaches (Onishi & Kiyama. Nucl. Acids Res.29, 3448–3457, 2001; Onishi & Kiyama J. Biol. Chem.278, 8163–8171, 2003; Kato et al. J. Mol. Biol.332, 111–125, 2003; Wanapirak et al. J. Mol. Evol.56, 649–657, 2003; Onishi & Kiyama. Recent Res. Devel. Nucl. Acids in press). The element is characterized by the appearance of AA- or TT-dinucleotides in the A+T-rich region located 200 to 400 bp upstream of cap sites. G tracts 3 to 5 nucleotides long exist between the A+T-rich region and the conserved transcription factor binding sites (GATA-1 site and the CACCC, CCAAT, and ATA boxes). An average periodicity of AA- or TT- dinucleotides in the region from a total of eighteen β-family globin genes from four species was approximately 13 bp, suggesting DNA in these regions to show right-handed superhelicity. A proposed biological meaning of this element is to adjust the spatial positions for the first interaction of the transcription factors which should recognize specific DNA sequences in the presence of packed chromatin.
- Published
- 2004
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