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Genes for beta-thromboglobulin and platelet factor 4 are closely linked and
form part of a cluster of related genes on chromosome 4
A Tunnacliffe, S Majumdar, B Yan and M Poncz
Department of Pathology, University of Cambridge, UK.
The small inducible gene (SIG) family encodes related proteins that are
involved in the overlapping processes of coagulation, inflammation, immune
response, and wound repair. This family contains two branches, termed CXC
and CC, which are distinguished by whether or not the first two of four
conserved cysteine residues are separated by an additional amino acid
residue. All of the CXC SIGs map to chromosome 4, including those encoding
beta-thromboglobulin (beta TG) and platelet factor 4 (PF4), both of which
are expressed by megakaryocytes in a tissue- specific fashion. Both of
these latter two genes have been previously reported to be duplicated,
there being a PF4 and a PF4alt gene, and a beta TG1 and beta TG2 gene. We
now show by pulse-field gel electrophoresis (PFGE) that the beta TG genes
are closely linked to the PF4 genes and to other previously mapped CXC
SIGs, namely IL8 (encoding interleukin-8), GRO1 (encoding a cytokine also
called melanoma growth- stimulatory activity), and two related genes GRO2
and GRO3, on a single 700-kb Sfil fragment localized to chromosome bands
4q12-q13. The only CXC SIG not linked to this cluster is that encoding
gamma-interferon- induced 10-Kd protein (INP10), which has been previously
localized to 4q21. Analysis of lambda genomic clones demonstrate that the
beta TG1 and PF4 genes are separated by less than 7 kb, and the beta TG2
and PF4alt genes by approximately 5 kb. Within each beta TG/PF4
duplication, the beta TG-like gene is upstream of its linked PF4-like gene.
Thus, the beta TG/PF4 genes appear to form a close-linked complex expressed
in a megakaryocyte-specific fashion. Further genomic studies may provide
additional insights into the regulation of the tissue- specific expression
of the beta TG/PF4 gene complex, while further analysis of the linked CXC
SIG cytokine family may provide further understanding of their evolutionary
history.
Volume 79,
Issue 11,
pp. 2896-2900,
06/01/1992
Copyright © 1992 by The American Society of Hematology
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