title: Multifunctional transcription factor TFII-I is an activator of BRCA1 function.
abstract: BACKGROUND
  The TFII-I is a multifunctional transcriptional factor known to bind specifically to several DNA sequence elements and to mediate growth factor signalling. A microdeletion at the chromosomal location 7q11.23 encoding TFII-I and the related family of transcription factors may result in the onset of Williams-Beuren syndrome, an autosomal dominant genetic disorder characterised by a unique cognitive profile, diabetes, hypertension, anxiety, and craniofacial defects. Hereditary breast and ovarian cancer susceptibility gene product BRCA1 has been shown to serve as a positive regulator of SIRT1 expression by binding to the promoter region of SIRT1, but cross talk between BRCA1 and TFII-I has not been investigated to date.
  
  
  METHODS
  A physical interaction between TFII-I and BRCA1 was explored. To determine pathophysiological function of TFII-I, its role as a transcriptional cofactor for BRCA1 was investigated.
  
  
  RESULTS
  We found a physical interaction between the carboxyl terminus of TFII-I and the carboxyl terminus of BRCA1, also known as the BRCT domain. Endogenous TFII-I and BRCA1 form a complex in nuclei of intact cells and formation of irradiation-induced nuclear foci was observed. We also showed that the expression of TFII-I stimulates the transcriptional activation function of BRCT by a transient expression assay. The expression of TFII-I also enhanced the transcriptional activation of the SIRT1 promoter mediated by full-length BRCA1.
  
  
  CONCLUSIONS
  These results revealed the intrinsic mechanism that TFII-I may modulate the cellular functions of BRCA1, and provide important implications to understand the development of breast cancer.
authors.affiliation: Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Tanikawa
authors.forename: O
authors.initials: O
authors.lastname: Wada-Hiraike
authors.forename: S
authors.initials: S
authors.lastname: Nakagawa
authors.forename: A
authors.initials: A
authors.lastname: Shirane
authors.forename: H
authors.initials: H
authors.lastname: Hiraike
authors.forename: S
authors.initials: S
authors.lastname: Koyama
authors.forename: Y
authors.initials: Y
authors.lastname: Miyamoto
authors.forename: K
authors.initials: K
authors.lastname: Sone
authors.forename: T
authors.initials: T
authors.lastname: Tsuruga
authors.forename: K
authors.initials: K
authors.lastname: Nagasaka
authors.forename: Y
authors.initials: Y
authors.lastname: Matsumoto
authors.forename: Y
authors.initials: Y
authors.lastname: Ikeda
authors.forename: K
authors.initials: K
authors.lastname: Shoji
authors.forename: K
authors.initials: K
authors.lastname: Oda
authors.forename: H
authors.initials: H
authors.lastname: Fukuhara
authors.forename: K
authors.initials: K
authors.lastname: Nakagawa
authors.forename: S
authors.initials: S
authors.lastname: Kato
authors.forename: T
authors.initials: T
authors.lastname: Yano
authors.forename: Y
authors.initials: Y
authors.lastname: Taketani
mesh_terms: D000818:Animals; D019313:BRCA1 Protein / Q000378:metabolism / Q000502:physiology*; D019556:COS Cells; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism / Q000473:pathology; D002522:Chlorocebus aethiops; D004249:DNA Damage / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D006801:Humans; D011485:Protein Binding; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism / Q000502:physiology; D019473:Transcription Factors, TFII / Q000378:metabolism / Q000502:physiology*; D015533:Transcriptional Activation / Q000502:physiology
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; C104259:GTF2I protein, human; D015534:Trans-Activators; D019473:Transcription Factors, TFII; C447939:SIRT1 protein, human; D056564:Sirtuin 1