Histone H1 subtype-specific consensus elements mediate cell cycle-regulated transcription in vitro.

Abstract

In this study we used nuclear extracts from centrifugally elutriated cell populations to study histone HI transcriptional regulation during the cell cycle. Analysis of mutations within the HI promoter establish that both of the HI subtype-specific consensus elements participate in induction of transcription upon entry into S phase. The DNA binding activity of H1TF2, which specifically interacts with the HI proximal subtype-specific element, is increased in S-phase nuclear extracts, whereas no increase in DNA binding is observed for the HI distal subtype-specific DNA transcription factor HlTFl or the H2b subtype-specific factor OTFl. These data strongly support the idea that histone gene subtype-specific transcription factors are important for S-phasedependent expression of histone genes. Further studies of these factors will be important for increased understanding of the transition from G^ to S phase of the mammalian cell cycle.[Key Words: Cell cycle; histone genes; in vitro transcription; centrifugal elutriation; transcription factors] Received July 11, 1989; revised version accepted September 7, 1989.The transition from Gi to S phase in the eukaryotic cell cycle results in the activation of chromosomal DNA synthesis and the increased production of a variety of activities required for synthesis or packaging of nascent DNA. The synthesis of most histone proteins is dramat ically induced at this time (Robbins and Borum 1967), because of both increased rates of transcription of the individual histone genes and accelerated post-transcriptional histone mRNA accumulation (Heintz et al. 1983;Sittman et al. 1983). Recent studies of the mechanisms regulating histone gene transcription demonstrated that promoter proximal DNA sequences (Artishevsky et al. 1987;Dalton and Wells 1988a;La Bella et al. 1988) and their cognate transcription factors (Fletcher et al. 1987;Dalton and Wells 1988b) are crucial for increased tran scription during S phase. It is our belief that a detailed knowledge of these proteins and their changing activi ties during S phase can lead to fundamental advances in our understanding of the cell cycle.The most specific information concerning the regula tion of histone gene expression during S phase has been obtained by analysis of histone H2b gene expression. We have demonstrated that a very highly conserved sub type-specific consensus element, containing the core octanucleotide ATTTGCAT and positioned immediately upstream from the TATA element, mediates cell-cycle regulation of H2b transcription (La Bella et al. 1988). The transcription factor that specifically interacts with this regulatory element has been purified and characterized ^Corresponding author. (Fletcher et al. 1987), although the precise mechanism by which this factor contributes to the S-phase induc tion of H2b transcription is not yet known. The H2b cell-cycle regulatory element is not present in genes en coding other histone subtypes. However, comparison of the H4, H2b, and HI promoters reveals that each pro moter contains a highly co...

Role of a distal promoter element in the S‐phase control of the human H1.2 histone gene transcription

“…They showed a decrease in S-phase-dependent transcriptional induction compared with cells in G,, upon removal of either the H1 or CCAAT box. In contrast to Dalton and Wells [13] they did not observe an increase of the H1-box-binding factor HlTFl at S phase.…”

“…This conclusion was based on run-off transcription, H1-box mutation, gel mobility-shift assays and DNase protection studies [12]. Gallinari et al [13], however, concentrated on the cooperative action of factors binding to the H1 and CCAAT boxes. They showed a decrease in S-phase-dependent transcriptional induction compared with cells in G,, upon removal of either the H1 or CCAAT box.…”

“…Its involvement in the S-phase-dependent transcription of chicken [12] and human [13] H1 genes has been demonstrated by deletion analysis [12] and factor titration throughout the cell cycle [13]. We have extended the functional analysis of the human H1.2 (for nomenclature, see [2]) gene promoter including more distal promoter sites.…”

Conserved sequence elements in human main type‐H1 histone gene promoters : their role in H1 gene expression

“…However, the authors concluded that other sequences in the proximal promoter may contribute to the increased transcription of H1 genes during the S phase. Up to now, attempts to purify the trans-acting factor that putatively interacts with the H1 box (termed either H1-SF [26] or H1TF1 [45]) were without success.…”

Organization and expression of H1 histone and H1 replacement histone genes

“…Van Wijnen et al [1988a, bl and Gallinari et al [19891 have identified additional H1 specific transcription factors (termed HiNF-B or HlTF2, they may be identical), which both interact with the CCAAT-sequence. DNA binding studies indicate that the CCAAT box binding factor plays a major role in the S-phase regulation, since the HlTF2 activity is increased in S-phase nuclear extracts [La Bella et al, 1989;Heintz, 19911. As shown in Figure 1, the CCAAT box is missing in Hl0/H5-type gene promoters but is present in the upstream regions of H l t and main type H1 genes.…”