GSBS Student Publications


Altered binding of human histone gene transcription factors during the shutdown of proliferation and onset of differentiation in HL-60 cells

UMMS Affiliation

Graduate School of Biomedical Sciences; Department of Cell Biology



Document Type


Medical Subject Headings

Base Sequence; Binding Sites; Cell Cycle; Cell Differentiation; Cell Division; DNA; Gene Expression Regulation; Histones; Humans; Leukemia, Promyelocytic, Acute; Molecular Sequence Data; Promoter Regions (Genetics); Transcription Factors; Transcription, Genetic; Tumor Cells, Cultured


Life Sciences | Medicine and Health Sciences


Two sites of protein-DNA interaction have been identified in vivo and in vitro in the proximal promoter regions of an H4 and an H3 human histone gene. In proliferating cells, these genes are transcribed throughout the cell cycle, and both the more distal site I and the proximal site II are occupied by promoter-binding factors. In this report we demonstrate that during the shutdown of proliferation and onset of differentiation of the human promyelocytic leukemia cell line HL-60 into cells that exhibit phenotypic properties of monocytes, histone gene expression is down-regulated at the level of transcription. In vivo occupancy of site I by promoter factors persists in the differentiated HL-60 cells, but protein-DNA interactions at site II are selectively lost. Furthermore, in vitro binding activity of the site II promoter factor HiNF-D is lost in differentiated cells, and nuclear extracts from differentiated cells do not support in vitro transcription of these histone genes. Our results suggest that the interaction of HiNF-D with proximal promoter site II sequences plays a primary role in rendering cell growth-regulated histone genes transcribable in proliferating cells. It appears that while cell-cycle control of histone gene expression is mediated by both transcription and mRNA stability, with the shutdown of proliferation and onset mRNA stability, with the shutdown of proliferation and onset of differentiation, histone gene expression is regulated at the transcriptional level.

Rights and Permissions

Citation: Proc Natl Acad Sci U S A. 1989 Mar;86(6):1865-9.

Related Resources

Link to Article in PubMed

Journal Title

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

PubMed ID