GSBS Student Publications

Title

Modifications of protein-DNA interactions in the proximal promoter of a cell-growth-regulated histone gene during onset and progression of osteoblast differentiation

UMMS Affiliation

Graduate School of Biomedical Sciences; Department of Cell Biology

Date

7-1-1990

Document Type

Article

Medical Subject Headings

Animals; Base Sequence; *CCAAT-Enhancer-Binding Proteins; Cell Differentiation; DNA-Binding Proteins; Fetus; *Gene Expression Regulation; *Genes; Histones; Humans; Mice; Molecular Sequence Data; Nuclear Proteins; Osteoblasts; *Promoter Regions (Genetics); Protein Binding; Rats; Sequence Homology, Nucleic Acid

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

A temporal sequence of interrelated cellular, biochemical, and molecular events which occurs during the progressive expression of the differentiated osteoblast phenotype in primary cultures of fetal rat calvarial cells results in the development of a bone-tissue-like organization. This ordered developmental sequence encompasses three periods: proliferation, matrix maturation, and mineralization. Initially, the cells actively proliferate and synthesize type I collagen. This is followed by a period of matrix organization and maturation and then by a period of extracellular matrix mineralization. At the completion of proliferation, when expression of osteoblast phenotype markers such as alkaline phosphatase is observed, the cell-cycle-related histone genes are down-regulated transcriptionally, suggesting that a key signaling mechanism at this transition point involves modifications of protein-DNA interactions in the regulatory elements of these growth-regulated genes. Our results demonstrate that there is a selective loss of interaction of the promoter binding factor HiNF-D with the site II region of an H4 histone gene proximal promoter that regulates the specificity and level of transcription only when the down-regulation of proliferation is accompanied by modifications in the extracellular matrix that contribute to progression of osteoblast differentiation. Thus, this specific loss of protein-DNA interaction serves as a marker for a key transition point in the osteoblast developmental sequence, where the down-regulation of proliferation is functionally coupled to the appearance of osteoblast phenotypic properties associated with the organization and maturation of an extracellular matrix that becomes competent to mineralize.

Rights and Permissions

Citation: Proc Natl Acad Sci U S A. 1990 Jul;87(13):5129-33.

Related Resources

Link to article in PubMed

Journal Title

Proceedings of the National Academy of Sciences of the United States of America

PubMed ID

2367528