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PMID: 1620129 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Overlapping and CpG methylation-sensitive protein-DNA interactions at the histone H4 transcriptional cell cycle domain: distinctions between two human H4 gene promoters.

Molecular and cellular biology ·Vol. 12 ·No. 7 ·1992-07-00 ·Pages 3273-87

van Wijnen AJ, van den Ent FM, Lian JB, Stein JL, Stein GS

Abstract

Transcriptional regulation of vertebrate histone genes during the cell cycle is mediated by several factors interacting with a series of cis-acting elements located in the 5' regions of these genes. The arrangement of these promoter elements is different for each gene. However, most histone H4 gene promoters contain a highly conserved sequence immediately upstream of the TATA box (H4 subtype consensus sequence), and this region in the human H4 gene FO108 is involved in cell cycle control. The sequence-specific interaction of nuclear factor HiNF-D with this key proximal promoter element of the H4-FO108 gene is cell cycle regulated in normal diploid cells (J. Holthuis, T.A. Owen, A.J. van Wijnen, K.L. Wright, A. Ramsey-Ewing, M.B. Kennedy, R. Carter, S.C. Cosenza, K.J. Soprano, J.B. Lian, J.L. Stein, and G.S. Stein, Science, 247:1454-1457, 1990). Here, we show that this region of the H4-FO108 gene represents a composite protein-DNA interaction domain for several distinct sequence-specific DNA-binding activities, including HiNF-D, HiNF-M, and HiNF-P. Factor HiNF-P is similar to H4TF-2, a DNA-binding activity that is not cell cycle regulated and that interacts with the analogous region of the H4 gene H4.A (F. LaBella and N. Heintz, Mol. Cell. Biol. 11:5825-5831, 1991). The H4.A gene fails to interact with factors HiNF-M and HiNF-D owing to two independent sets of specific nucleotide variants, indicating differences in protein-DNA interactions between these H4 genes. Cytosine methylation of a highly conserved CpG dinucleotide interferes with binding of HiNF-P/H4TF-2 to both the H4-FO108 and H4.A promoters, but no effect is observed for either HiNF-M or HiNF-D binding to the H4-FO108 gene. Thus, strong evolutionary conservation of the H4 consensus sequence may be related to combinatorial interactions involving overlapping and interdigitated recognition nucleotides for several proteins, whose activities are regulated independently. Our results also suggest molecular complexity in the transcriptional regulation of distinct human H4 genes.

MeSH Terms
Base Sequence Binding, Competitive Cell Cycle/genetics DNA-Binding Proteins/metabolism Gene Expression Regulation Histones/genetics Humans Interferon Regulatory Factor-2 Methylation Methyltransferases/metabolism Molecular Sequence Data Mutagenesis, Site-Directed Oligonucleotides/metabolism Promoter Regions, Genetic/genetics Repressor Proteins Sequence Homology, Nucleic Acid Substrate Specificity Tissue Distribution Transcription Factors Transcription, Genetic
Chemicals
DNA-Binding Proteins HINF-D protein, human Histones IRF2 protein, human Interferon Regulatory Factor-2 Oligonucleotides Repressor Proteins Transcription Factors Methyltransferases
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
van Wijnen A J
Department of Cell Biology, University of Massachusetts Medical Center, Worcester 01655.
van den Ent F M
Lian J B
Stein J L
Stein G S
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/mcb.12.7.3273-3287.1992
Published
1992-07-00
Pages
3273-87
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC364541
Subset
IM
Grants
NIGMS NIH HHS · GM32010 · United States
External Links
PubMed source DOI: 10.1128/mcb.12.7.3273-3287.1992 PMC Full Text View journal details
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