Novel PAX6 binding sites in the human genome and the role of repetitive elements in the evolution of gene regulation

被引：30

作者：

Zhou, YH

Zheng, JB

Gu, X

Saunders, GF

Yung, WKA

机构：

[1] Univ Texas, MD Anderson Canc Ctr, Dept Neurooncol, Houston, TX 77030 USA

[2] Univ Texas, MD Anderson Canc Ctr, Dept Biochem & Mol Biochem, Houston, TX 77030 USA

[3] Iowa State Univ Sci & Technol, Dept Zool Genet, Iowa Computat Biol Lab, Ames, IA 50011 USA

[4] Iowa State Univ Sci & Technol, Ctr Bioinformat & Biol Stat, Iowa Computat Biol Lab, Ames, IA 50011 USA

来源：

GENOME RESEARCH | 2002年 / 12卷 / 11期

关键词：

D O I：

10.1101/gr.188302

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Pax6 is a critical transcription factor in the development of the eye, pancreas, and central nervous system. It is composed of two DNA-binding domains, the paired domain (PD), which has two helix-turn-helix (HTH) motifs, and the homeodomain (HD), made up from another HTH motif. Each HTH motif can bind to DNA separately or in combination with the others. We identified three novel binding sites that are specific for the PD and HD domains of human PAX6 from single-copy human genomic DNA libraries using cyclic amplification of protein binding sequences (CAPBS) and electrophoretic mobility shift assays (EMSAs). One of the binding sites was found within sequences of repetitive Alu elements. However, most of the Alu sequences were unable to bind to PAX6 because of a small number of mismatches (mostly in CpG dinucleoticle hot spots) in the consensus Alu sequences. PAX6 binding Alu elements are found primarily in old and intermediate-aged Alu subfamilies. These data along with Our previously identified B1-type Pax6 binding site showed that evolutionarily conserved Pax6 has target sites that are disparate in primates and rodents. This difference indicates that human and mouse Pax6-reglulated gene networks may have evolved through these linea.-e-specific repeat elements. [The sequence data from this Study have been Submitted to GenBank under accession no. AF451322. The following individual kindly provided reagents, samples, or unpublished information as indicated in this paper: L. Yu.]

引用

页码：1716 / 1722

页数：7

共 34 条

[1]

Aalfs C.M., Fantes J.A., Wenniger-Prick L.J., Sluijter S., Hennekam R.C., van Heyningen V., Hoovers J.M., Tandem duplication of 11p12-p13 in a child with borderline development delay and eye abnormalities: Dose effect of the PAX6 gene product?, Am. J. Med. Genet, 73, pp. 267-271, (1997)

[2]

Batzer M.A., Deminger P.L., Hellmann-Blumberg U., Jurka J., Labuda D., Rubin C.M., Schmid C.W., Zietkiewicz E., Zuckerkandl E., Standardized nomenclature for Alu repeats, J. Mol. Evol, 42, pp. 3-6, (1996)

[3]

Britten R.J., DNA sequence insertion and evolutionary variation in gene regulation, Proc. Natl. Acad. Sci, 93, pp. 9374-9377, (1996)

[4]

Britten R.J., Baron W.F., Stout D.B., Davidson E.H., Sources and evolution of human Alu repeated sequences, Proc. Natl. Acad. Sci, 85, pp. 4770-4774, (1988)

[5]

Callaerts P., Halder G., Gehring W.J., Pax6 in development and evolution, Annu. Rev. Neurosci, 20, pp. 483-532, (1997)

[6]

Dahl E., Koseki H., Balling R., Pax genes and organogenesis, Bioessays, 19, pp. 755-765, (1997)

[7]

Dsouza M., Larsen N., Overbeek R., Searching for patterns in genomic data, Trends Genet, 13, pp. 497-498, (1997)

[8]

Engelkamp D., Rashbass P., Seawright A., van Heyningen V., Role of Pax6 in development of the cerebellar system, Development, 126, pp. 3585-3596, (1999)

[9]

Epstein J., Glaser T., Cai J., Jepeal L., Walton D., Maas R., Two independent and interactive DNA-binding subdomains of the Pax6 paired domain are regulated by alternative splicing, Genes & Dev, 8, pp. 2022-2034, (1994)

[10]

Epstein J., Cai J., Glaser T., Jepeal L., Maas R., Identification of a Pax paired domain recognition sequence and evidence for DNA-dependent conformational changes, J. Biol. Chem, 269, pp. 8355-8361, (1994)

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