Histone Gene Transcription Factor Binding in Extracts of Normal Human Cells

Abstract

Transcriptional regulation of mammalian histone genes during S phase is achieved through activation of specific factors which interact with subtype-specific histone gene promoter sequences. It has previously been shown that in HeLa cells this induction is not mediated by obligatory changes in the DNA binding activity of histone gene transcription factors as cells progress through the cell cycle. Recently, it has been reported that the DNA binding properties of a putative histone gene transcription factor may be quite different in normal and transformed cells (J. Holthuis, T. A. Owen, A. J. van Wijnen, K. L. Wright, A. Ramsey-Ewing, M. B. Kennedy, R. Carter, S. C. Cosenza, K. J. Soprano, J. B. Lian, J. L. Stein, and G. S. Stein, Science 247:1454-1457, 1990). To determine whether the properties of well-characterized histone gene transcription factors are altered in transformed versus normal ceUs, we have examined the DNA binding activity of human histone transcription factors during the WI38 (a primary line of normal human fetal lung fibroblasts) cell cycle. The results demonstrate that the properties of Oct1, H4TF1, and H4TF2 are similar in WI38 and HeLa cells and that their DNA binding activities are constitutive during interphase of both normal and transformed cell lines. Although it remains possible that these factors are directly or indirectly perturbed as a result of cellular transformation, it appears unlikely that transformation results in gross changes in DNA binding activity as cells progress toward division.