Title

Repressor elements in the coding region of the human histone H4 gene interact with the transcription factor CDP/cut

UMMS Affiliation

Graduate School of Biomedical Sciences; Department of Cell Biology

Date

1-5-1999

Document Type

Article

Medical Subject Headings

Base Sequence; Binding Sites; Cell Cycle; Cell Division; DNA; Genes; Histones; Homeodomain Proteins; Humans; Nuclear Proteins; Regulatory Sequences, Nucleic Acid; Repressor Proteins; Sequence Homology, Nucleic Acid; Transcription Factors; Transcription, Genetic

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

The coding region of the human histone H4 gene FO108 undergoes dynamic changes in chromatin structure that correlate with modifications in gene expression. Such structural alterations generally reflect transcription factor interactions with gene regulatory sequences. To test for regulatory elements within the coding region, we performed transient transfection experiments in HeLa cells using constructs with histone H4 sequences fused upstream of a heterologous thymidine kinase promoter and CAT reporter gene. H4 gene sequences from -10 to +210 repressed transcription 4.8-fold. Further deletion and mutational analysis delineated three repressor elements within this region. Using oligonucleotide competition analysis and specific antibody recognition in electrophoretic mobility shift assays, as well as methylation interference and DNase I footprinting analyses, we have identified the CCAAT displacement protein (CDP/cut) as the factor that interacts with these three repressor elements. CDP/cut binding to these repressor sites is proliferation-specific and cell-cycle-regulated, increasing in mid to late S phase. Our results indicate that the proximal 200 nucleotides of the histone H4-coding region contain transcriptional regulatory elements that may contribute to cell-cycle control of histone gene expression by interacting with repressor complexes containing CDP/cut homeodomain transcription factors.

Rights and Permissions

Citation: Gene. 1998 Oct 23;221(2):267-77.

Related Resources

Link to article in PubMed

PubMed ID

9874597