The mechanisms of transcriptional activation in heterochromatin were investigated by using FISH to directly visualize changes in chromatin organization during activation of a heterochromatic lambda5 transgene. A DNase I hypersensitive site was shown to relocate the transgene to the outside of the pericentromeric heterochromatin complex in the absence of transcription. Activation of transcription, which is dependent on the transcription factor EBF, occurs in a stochastic manner that resembles telomeric silencing in yeast, with the transcribed gene remaining closely associated with the heterochromatin complex. Reducing the dosage of EBF results in a reduced frequency of localization of the transgene to the outside of the heterochromatin complex and lower levels of transcription. These data provide evidence that transcription factors can initiate changes in higher order chromatin structure during the earliest stages of gene activation.
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Univ Bradford, Ctr Skin Sci, Bradford BD7 1DP, W Yorkshire, EnglandUniv Bradford, Ctr Skin Sci, Bradford BD7 1DP, W Yorkshire, England
Fessing, M. Y.
Rapisarda, V.
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Univ Bradford, Ctr Skin Sci, Bradford BD7 1DP, W Yorkshire, EnglandUniv Bradford, Ctr Skin Sci, Bradford BD7 1DP, W Yorkshire, England
Rapisarda, V.
Mardaryev, A. N.
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Univ Bradford, Ctr Skin Sci, Bradford BD7 1DP, W Yorkshire, EnglandUniv Bradford, Ctr Skin Sci, Bradford BD7 1DP, W Yorkshire, England
Mardaryev, A. N.
Gdula, M. R.
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Boston Univ, Boston, MA 02215 USAUniv Bradford, Ctr Skin Sci, Bradford BD7 1DP, W Yorkshire, England
Gdula, M. R.
Sharov, A. A.
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Boston Univ, Boston, MA 02215 USAUniv Bradford, Ctr Skin Sci, Bradford BD7 1DP, W Yorkshire, England
Sharov, A. A.
Karakesisoglou, I.
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Univ Durham, Sch Biol Sci, Durham, EnglandUniv Bradford, Ctr Skin Sci, Bradford BD7 1DP, W Yorkshire, England
Karakesisoglou, I.
Hutchison, C. J.
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Univ Durham, Sch Biol Sci, Durham, EnglandUniv Bradford, Ctr Skin Sci, Bradford BD7 1DP, W Yorkshire, England
Hutchison, C. J.
Botchkarev, V. A.
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Univ Bradford, Ctr Skin Sci, Bradford BD7 1DP, W Yorkshire, England
Boston Univ, Boston, MA 02215 USAUniv Bradford, Ctr Skin Sci, Bradford BD7 1DP, W Yorkshire, England