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Assignment of the Steroid
Receptor Coactivator-1 (SRC-1)
Gene to Human Chromosome
Band 2p23
Melina Carapeti,* Ricardo C. T. Aguiar,²
Andrew Chase,* John M. Goldman,*
and Nicholas C. P. Cross*
,1
* Department of Haematology, Imperial College School of Medicine,
Hammersmith Hospital, Du Cane Road, London W12 ONN, United
Kingdom; and ² Division of Hematologic Malignancies, Dana Farber
Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115
Received March 16, 1998; accepted June 9, 1998
Nuclear receptor coactivators (NRCoAs) mediate the li-
gand-dependent transcriptional activation of specific genes
by nuclear receptors, for example, the receptors for steroid
and thyroid hormones, retinoids, and vitamin D. Currently,
three NRCoAs have been cloned: TIF2 (also known as GRIP1
or NCoA-2) (11), SRC-1 (also known as F-SRC-1 or NCoA-1)
(8), and AIB1 (also known as RAC3, ACTR, or p/CIP) (2).
These proteins are functionally and structurally homologous
and are thought to stimulate gene expression by facilitating
the assembly of basal transcription factors into a stable
preinitiation complex. Recently NRCoAs have been shown to
possess histone acetyl transferase (HAT) activity and also to
interact directly with CBP, a general transcriptional co-inte-
grator (10). It is likely, therefore, that NRCoAs mediate tran-
scriptional activation by a mechanism that involves chroma-
tin remodeling.
Several lines of evidence have implicated abnormalities of
NRCoAs in malignancy. The AIB1 gene at 20q12 is fre-
quently amplified in breast and ovarian cancers (2), and we
have recently cloned a novel fusion between the TIF2 and the
MOZ genes at 8q13 and 8p11, respectively, in acute myeloid
leukemia (AML) (1, 3). In addition, the ARA
70
gene was
shown to be fused to RET in a case of human thyroid papil-
lary carcinoma (9, 12), and TIF1 is fused to B-RAF in the
mouse hepatoma-derived oncogene T18 (5). Although ARA
70
and TIF1 do not share sequence homology with the NRCoA
family, they are also involved in the ligand-dependent acti-
vation function of nuclear receptors.
Here we have mapped the chromosomal localization of
SRC-1 (GenBank Accession No. U40396) to determine
whether this gene is also located at a region that has been
implicated in malignancy. An SRC-1 probe, designed to a
region of low homology between the NRCoA family mem-
bers, was amplified from normal peripheral blood leukocyte
cDNA with primers SRC1-A (5'-CTGAGCTAGCTGAACTA-
GAC-3') and SRC1-B (5'-GGTGCTGTTGACTGTACAGT-3').
The probe was sequenced to confirm its identity and used to
screen the gridded human library RPCI1. Four positive PAC
clones (Nos. 100-G8, 115-I1, 125-H2, and 200-P18) were iso-
lated and used as fluorescence in situ hybridization (FISH)
probes on metaphases from phytohemagglutinin-stimulated pe-
ripheral blood lymphocytes from a normal individual. PACs
were labeled with digoxigenin by nick-translation and detected
with sheep anti-digoxigenin (Boehringer-Mannheim, Germa-
ny), rabbit anti-sheep fluorescein isothiocyanate (FITC; Vector,
UK), and finally swine anti-rabbit FITC (Dako, UK). All four
PACs specifically hybridized to chromosome band 2p23 and
to no other region (Fig. 1A). A gridded CEPH mega-YAC
library was also screened with the SRC-1 probe. Several
positive clones were identified, including Nos. 744h7, 765d3,
916f8, and 953d6. Comparison with the existing map of chro-
mosome 2 (4) indicates that SRC-1 maps to the short arm in
the vicinity of markers D2S144 and D2S171 (Fig. 1B). These
markers have been mapped to 48 cM and 149 cR of the
genetic and radiation hybrid maps, respectively, and are
contained in the contig WC2.2 (http://www.genome.wi.mit.
edu:80/cgi-bin/contig/lookup_contig).
Translocations involving chromosome 2p23 or neighboring
bands have been reported in a variety of hematological ma-
lignancies (6). The ALK gene at 2p23 is disrupted by t(2;
5)(p23;q35) in anaplastic large-cell lymphoma (7), but the
molecular etiology of other translocations, for example, the
t(2;3)(p23;q26) in AML, is unknown. The mapping of SRC-1 to
2p23 provides a further candidate gene for disruption by
these translocations.
ACKNOWLEDGMENTS
We thank the Medical Research Council Human Genome Mapping
Project (MRC HGMP) Resource Centre (Hinxton, UK) for providing
the PAC clones and CEPH megaYAC clones.
REFERENCES
1. Aguiar, R. C. T., Chase, A., Coulthard, S., Macdonald, D. H. C.,
Carapeti, M., Reiter, A., Sohal, J., Lennard, A., Goldman, J. M.,
and Cross, N. C. P. (1997). Abnormalities of chromosome band
1
To whom correspondence should be addressed. Telephone: + 44
181 383 3302. Fax: + 44 181 740 9679. E-mail: ncross@rpms.ac.uk.
242 BRIEF REPORTS
GENOMICS 52, 242–244 (1998)
ARTICLE NO. GE985446
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