Title

Downregulation of histone H4 gene transcription during postnatal development in transgenic mice and at the onset of differentiation in transgenically derived calvarial osteoblast cultures

Student Author(s)

Andre Van Wijnen

GSBS Program

Cell Biology

UMMS Affiliation

Department of Cell Biology

Date

6-1-1992

Document Type

Article

Medical Subject Headings

Aging; Animals; Cell Differentiation; Cells, Cultured; Chloramphenicol O-Acetyltransferase; *Down-Regulation; Female; Histones; Mice; Mice, Transgenic; Osteoblasts; Promoter Regions (Genetics); RNA, Messenger; Recombinant Fusion Proteins; Skull; Tissue Distribution; *Transcription, Genetic

Disciplines

Cell Biology | Life Sciences | Medicine and Health Sciences

Abstract

In vivo regulation of cell cycle dependent human histone gene expression was examined in transgenic mice using a fusion construct containing 6.5 kB of a human H4 promoter linked to the chloramphenicol acetyltransferase (CAT) reporter gene. Transcriptional control of histone gene expression, as a function of proliferative activity, was determined. We established the relationship between DNA replication dependent H4 mRNA levels (Northern blot analysis) and H4 promoter activity (CAT assay) during postnatal development in a broad spectrum of tissues. In most tissues sampled in adult animals, the cellular representation of H4 gene transcripts declined in parallel with promoter activity. This result is consistent with transcriptional control of H4 gene expression at the cessation of proliferation. Interestingly, while H4 mRNA was detectable at very low levels post-proliferatively in brain, promoter activity persisted in adult brain, where most of the cells are terminally differentiated. This dissociation between histone gene promoter activity and histone mRNA accumulation points to the possibility of post-transcriptional regulation of histone gene expression in brain. Cultures of osteoblasts were prepared from calvaria of transgenic mice carrying the H4 promoter/CAT reporter construct. In contrast to the brain, in these bone-derived cells, we established by immunohistochemistry that the transition to the quiescent, differentiated state is associated with a transcriptionally mediated downregulation of histone gene expression at the single cell level.

Rights and Permissions

Citation: J Cell Biochem. 1992 Jun;49(2):137-47. Link to article on publisher's site

Related Resources

Link to article in PubMed