Accessibility of nuclear chromatin by DNA binding polyamides.
Chem Biol
; 10(9): 859-67, 2003 Sep.
Article
em En
| MEDLINE
| ID: mdl-14522056
ABSTRACT
Pyrrole-imidazole polyamides bind DNA with affinities comparable to those of transcriptional regulatory proteins and inhibit the DNA binding activities of components of the transcription apparatus. If polyamides are to be useful for the regulation of gene expression in cell culture experiments, one pivotal issue is accessibility of specific sites in nuclear chromatin. We first determined the kinetics of uptake and subcellular distribution of polyamides in lymphoid and myeloid cells using fluorescent polyamide-bodipy conjugates and deconvolution microscopy. Then cells were incubated with a polyamide-chlorambucil conjugate, and the sites of specific DNA cleavage in the nuclear chromatin were assayed by ligation-mediated PCR. In addition, DNA microarray analysis revealed that two different polyamides generated distinct transcription profiles. Remarkably, the polyamides affected only a limited number of genes.
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Base de dados:
MEDLINE
Assunto principal:
Transcrição Gênica
/
Cromatina
/
Nylons
Limite:
Humans
Idioma:
En
Revista:
Chem Biol
Assunto da revista:
BIOLOGIA
/
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2003
Tipo de documento:
Article
País de afiliação:
Estados Unidos