© 1999 American Heart Association, Inc.
Original Contributions |
BTEB2, a Krüppel-Like Transcription Factor, Regulates Expression of the SMemb/Nonmuscle Myosin Heavy Chain B (SMemb/NMHC-B) Gene
From The Second Department of Internal Medicine (N.W., M. Kurabayashi, Y.S., K.K.-K., Y.H., I.M., M.A., M. Kuro-o, R.N.), Gunma University School of Medicine, Gunma, and The Third Department of Internal Medicine (M.W., T.S., Y.Y.), University of Tokyo, Japan.
Correspondence to Ryozo Nagai, MD, The Second Department of Internal Medicine, Gunma University School of Medicine, 3-39-15 Showa-machi, Maebashi, Gunma, 375-8511, Japan. E-mail nagai{at}news.sb.gunma-u.ac.jp
We have recently characterized the promoter region of the
rabbit embryonic smooth muscle myosin heavy chain (SMemb/NMHC-B)
gene and identified the 15-bp sequence, designated SE1, located at
-105 from the transcriptional start site as an important regulatory
element for its transcriptional activity in a smooth muscle cell (SMC)
line. In this study, we attempted to isolate cDNA clones encoding for
the transcription factors that control the expression of the SMemb gene
through binding to this cis-regulatory element. We screened
a 
gt11 cDNA library prepared from C2/2 cells, a
rabbit-derived SMC line, by using a radiolabeled concatenated
oligonucleotide containing SE1 as a probe. Sequence
analysis revealed that one of the cDNA clones corresponds to
the rabbit homologue of basic transcriptional element binding protein-2
(BTEB2), which has previously been identified as one of the
Krüppel-like transcription factor. Gel mobility shift assays and
antibody supershift analyses with nuclear extracts from C2/2
cells indicate that BTEB2 is a major component of nuclear factor:SE1
complexes. Furthermore, a glutathione S-transferase-BTEB2
fusion protein binds to the SE1 in a sequence-specific manner. In
support of the functionality of BTEB2 binding, basal promoter activity
and BTEB2-induced transcriptional activation were markedly attenuated
by the disruption of the SE1. In adult rabbit tissues, BTEB2 mRNA was
most highly expressed in intestine, urinary bladder, and uterus. BTEB2
mRNA levels were downregulated in rabbit aorta during normal
development. Moreover, immunohistochemical analysis indicated a
marked induction of BTEB2 protein in the neointimal SMC
after balloon injury in rat aorta. These results suggest that BTEB2
mediates the transcriptional regulation of the SMemb/NMHC-B gene and
possibly plays a role in regulating gene expression during phenotypic
modulation of vascular SMC.
Key Words: SMemb/NMHC-B • smooth muscle cell • basic transcriptional element binding protein-2
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