This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Butner, K Articles by Lo, C W Search for Related Content PubMed PubMed Citation Articles by Butner, K Articles by Lo, C W

 Previous Article  |  Next Article 

Mol Cell Biol. 1986 December; 6(12): 4440-4449

Modulation of tk expression in mouse pericentromeric heterochromatin.

K Butner and C W Lo

ABSTRACT

We have obtained a mouse transformant cell line containing two herpes viral thymidine kinase (tk) genes integrated in pericentromeric heterochromatin. Restriction analysis of tk- revertant and tk+ rerevertant derivatives suggest that one of the two tk genes is repressed in tk- cells, but is reactivated in tk+ rerevertants. The results of Northern analysis indicated that repression-activation is probably controlled at the transcriptional level. To examine the molecular basis for this repression, we cloned the tk gene from a tk- revertant cell line. Then, using the cloned tk gene as donor DNA to select for tk+ transformants, we found that it has a transfection efficiency indistinguishable from the viral tk gene. This indicates that repression is probably not mediated via any DNA sequence changes within the tk gene. The results of further studies by restriction analysis, azacytidine treatments, and secondary DNA transfection assays demonstrated that tk repression is associated with changes in DNA methylation. Surprisingly, derepression of the tk gene was accompanied by rearrangements in the flanking DNA. The latter result suggests that the flanking DNA may exert cis effects on tk gene expression. Additional studies with this system may provide insights into the molecular basis underlying position effects in heterochromatin.

---

Mol Cell Biol. 1986 December; 6(12): 4440-4449

This article has been cited by other articles:

• Maillet, L, Boscheron, C, Gotta, M, Marcand, S, Gilson, E, Gasser, S M (1996). Evidence for silencing compartments within the yeast nucleus: a role for telomere proximity and Sir protein concentration in silencer-mediated repression.. Genes Dev. 10: 1796-1811 [Abstract]  
• Nicol, L, Jeppesen, P (1996). Chromatin organization in the homogeneously staining regions of a methotrexate-resistant mouse cell line: interspersion of inactive and active chromatin domains distinguished by acetylation of histone H4. J. Cell Sci. 109: 2221-2228 [Abstract]  
• Brachmann, C B, Sherman, J M, Devine, S E, Cameron, E E, Pillus, L, Boeke, J D (1995). The SIR2 gene family, conserved from bacteria to humans, functions in silencing, cell cycle progression, and chromosome stability.. Genes Dev. 9: 2888-2902 [Abstract]  
• Allshire, R C, Nimmo, E R, Ekwall, K, Javerzat, J P, Cranston, G (1995). Mutations derepressing silent centromeric domains in fission yeast disrupt chromosome segregation.. Genes Dev. 9: 218-233 [Abstract]  
• Loo, S, Rine, J (1994). Silencers and domains of generalized repression. Science 264: 1768-1771 [Abstract]  
• Manuelidis, L (1990). A view of interphase chromosomes. Science 250: 1533-1540 [Abstract]