Structural analysis of the human BIN1 gene: Evidence for tissue-specific transcriptional regulation and alternate RNA splicing

Robert Wechsler-Reya, Daitoku Sakamuro, Jing Zhang, James Duhadaway, George C. Prendergast

Research output: Contribution to journalArticle

106 Scopus citations

Abstract

BIN1 is a putative tumor suppressor that was identified through its interaction with the MYC oncoprotein. To begin to identify elements of BIN1 whose alteration may contribute to malignancy, we cloned and characterize the human BIN1 gene and promoter. Nineteen exons were identified in a region of >54 kilobases, six of which were alternately spliced in a cell type-specific manner. One alternately spliced exon encodes part of the MYC-binding domain, suggesting that splicing controls the MYC-binding capacity of BIN1 polypeptides. Four other alternately spliced exons encode amphiphysin- related sequences that were included in brain-specific BIN1 species, also termed amphiphysin isoforms or amphiphysin II. The 5'-flanking region of BIN1 is GC-rich and lacks a TATA box but directs transcriptional initiation from a single site. A ~0.9-kilobase fragment from this region was sufficient for basal transcription and transactivation by MyoD, which may account for the high levels of BIN1 observed in skeletal muscle. This study lays the foundation for genetic and epigenetic investigations into the role of BIN1 in normal and neoplastic cell regulation.

Original languageEnglish (US)
Pages (from-to)31453-31458
Number of pages6
JournalJournal of Biological Chemistry
Volume272
Issue number50
DOIs
StatePublished - Dec 12 1997
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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