Histone Gene Transcription During the Cell Cycle

Abstract

It has become evident during the last decade that periodic transcription of a wide variety of mRNAs is a critical component of the eucaryotic cell cycle. The first genes to be identified whose transcription is modulated during cell cycle progression were the histone genes (1). in vertebrates, the histone genes comprise a small gene family in which there are approximately a dozen genes encoding each of the four core histones (H4, H3, H2a, H2b), and approximately half that number encoding the linker histone H1 (2). Since histones are essential structural proteins, they are transcribed in most eucaryotic cells. However, in actively dividing cells their transcription is very tightly coupled to S phase of the cell cycle. Thus, as cells enter S phase, histone gene transcription is increased approximately ten fold, and as the cell exits S phase the rate of histone gene transcription returns to its pre-S phase levels. This tight coupling of histone gene transcription with DNA replication provides an opportunity to dissect molecular mechanisms of transcription that are responsive to specific cues during traverse through the cell cycle, and that may be essential for orderly progression toward division. The interest of our laboratory has been to define these transcriptional regulatory mechanisms, and to relate them to other critical events that are important for cell cycle regulation.