Abstract

This grant will support research designed to help answer the following questions: (1) What is the molecular mechanism of mammalian X-chromosome inactivation? (2) What is the biological function(s) of 5-methylcytosine in mammalian DNA? The working hypotheses that will guide this work are: (1) 5- Methylcytosine plays a significant role in mammalian gene regulation and cell differentiation, and (2) 5-Methylcytosine is an important component of the X-chromosome inactivation system.
The specific aims are to: (1) identify and study proteins that bind specifically, in vitro and in vivo, to X-linked promoters and X-chromosomal DNA, (2) prepare and study DNA methylated at cytosine residues in CpG doublets by human DNA methyltransferase, (3) study proteins that bind preferentially to enzymatically methylated DNA, and (4) determine the effect of methylation on proteins identified as a result of aim 1.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
9R01GM050575-06
Application #
3309492
Study Section
Mammalian Genetics Study Section (MGN)
Project Start
1988-07-01
Project End
1997-06-30
Budget Start
1993-07-01
Budget End
1994-06-30
Support Year
6
Fiscal Year
1993
Total Cost
Indirect Cost

  Institution

Name
City of Hope/Beckman Research Institute
Department
Type
DUNS #
City
Duarte
State
CA
Country
United States
Zip Code
91010

  Publications

Chen, Hsiu-Hua; Lebon, Jeanne; Riggs, Arthur D (2008) Analysis of RNA structure and RNA-protein interactions in mammalian cells by use of terminal transferase-dependent PCR. Methods Mol Biol 488:319-41
Chen, Zhao-Xia; Mann, Jeffrey R; Hsieh, Chih-Lin et al. (2005) Physical and functional interactions between the human DNMT3L protein and members of the de novo methyltransferase family. J Cell Biochem 95:902-17
Chen, Hsiu-Hua; Castanotto, Daniela; LeBon, Jeanne et al. (2004) In vivo detection of ribozyme cleavage products and RNA structure by use of terminal transferase-dependent PCR. Methods Mol Biol 252:109-24
Rodin, Sergei N; Riggs, Arthur D (2003) Epigenetic silencing may aid evolution by gene duplication. J Mol Evol 56:718-29
Shively, L; Chang, L; LeBon, J M et al. (2003) Real-time PCR assay for quantitative mismatch detection. Biotechniques 34:498-502, 504
Chong, Suyinn; Riggs, Arthur D; Bonifer, Constanze (2002) The chicken lysozyme chromatin domain contains a second, widely expressed gene. Nucleic Acids Res 30:463-7
Dai, S M; O'Connor, T R; Holmquist, G P et al. (2002) Ligation-mediated PCR: robotic liquid handling for DNA damage and repair. Biotechniques 33:1090-7
Chong, Suyinn; Kontaraki, Joanna; Bonifer, Constanze et al. (2002) A Functional chromatin domain does not resist X chromosome inactivation: silencing of cLys correlates with methylation of a dual promoter-replication origin. Mol Cell Biol 22:4667-76
Riggs, A D (2002) X chromosome inactivation, differentiation, and DNA methylation revisited, with a tribute to Susumu Ohno. Cytogenet Genome Res 99:17-24
Komura , J; Ikehata, H; Hosoi, Y et al. (2001) Mapping psoralen cross-links at the nucleotide level in mammalian cells: suppression of cross-linking at transcription factor- or nucleosome-binding sites. Biochemistry 40:4096-105

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