The architectural transcription factor high mobility group I(Y) participates in photoreceptor-specific gene expression

K. Y. Chau, N. Munshi, A. Keane-Myers, K. W. Cheung-Chau, A. Kwong-Fuk Tai, G. Manfioletti, C. K. Dorey, D. Thanos, D. J. Zack, S. J. Ono

Research output: Contribution to journalArticle

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Abstract

The nonhistone chromosomal proteins high mobility group I(Y) [HMG I(Y)] have been shown to function as architectural transcription factors facilitating enhanceosome formation on a variety of mammalian promoters. Specifically, they have been shown to act as a 'molecular glue' mediating protein-protein and protein-DNA contacts within the enhanceosome complex. HMG I(Y) proteins are expressed at high levels in embryonic and trans-formed cells and have been implicated in transcriptional regulation in these cells. Terminally differentiated cells, however, have been reported to express only minimal, if any, HMG I(Y). In contrast to these observations, we show here that adult mouse retinal photoreceptors, which are terminally differentiated cells, express high levels of these proteins. Using retinoblastoma cells as an approximate model, we further demonstrate in transiently transfected cells that inhibition of HMG I(Y) expression and mutation of HMG I(Y) binding sites significantly reduce rhodopsin promoter activity. DNase I footprint analysis indicates that HMG I protein interacts with a discrete site within the rhodopsin proximal promoter. This site overlaps with the binding site for Crx, a paired-like homeodomain transcription factor that is essential for photoreceptor functioning and that when mutated causes several forms of human photoreceptor degeneration. Both biochemical and functional experiments demonstrate that HMG I(Y) physically associate with Crx and that their interaction with DNA is required for high-level transcription of the rhodopsin gene. These data provide the first demonstration that HMG I(Y) can be important for gene activation in terminally differentiated cells.

Original languageEnglish (US)
Pages (from-to)7317-7324
Number of pages8
JournalJournal of Neuroscience
Volume20
Issue number19
StatePublished - Oct 1 2000

Fingerprint

Transcription Factors
Gene Expression
Rhodopsin
HMGA1a Protein
Proteins
Non Histone Chromosomal Proteins
Binding Sites
High Mobility Group Proteins
Vertebrate Photoreceptor Cells
Retinoblastoma
Deoxyribonuclease I
DNA
Adhesives
Transcriptional Activation
Mutation
Genes

Keywords

  • Crx
  • HMG I(Y)
  • Photoreceptors
  • Retina
  • Retinoblastoma
  • Rhodopsin

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Chau, K. Y., Munshi, N., Keane-Myers, A., Cheung-Chau, K. W., Kwong-Fuk Tai, A., Manfioletti, G., ... Ono, S. J. (2000). The architectural transcription factor high mobility group I(Y) participates in photoreceptor-specific gene expression. Journal of Neuroscience, 20(19), 7317-7324.

The architectural transcription factor high mobility group I(Y) participates in photoreceptor-specific gene expression. / Chau, K. Y.; Munshi, N.; Keane-Myers, A.; Cheung-Chau, K. W.; Kwong-Fuk Tai, A.; Manfioletti, G.; Dorey, C. K.; Thanos, D.; Zack, D. J.; Ono, S. J.

In: Journal of Neuroscience, Vol. 20, No. 19, 01.10.2000, p. 7317-7324.

Research output: Contribution to journalArticle

Chau, KY, Munshi, N, Keane-Myers, A, Cheung-Chau, KW, Kwong-Fuk Tai, A, Manfioletti, G, Dorey, CK, Thanos, D, Zack, DJ & Ono, SJ 2000, 'The architectural transcription factor high mobility group I(Y) participates in photoreceptor-specific gene expression', Journal of Neuroscience, vol. 20, no. 19, pp. 7317-7324.
Chau KY, Munshi N, Keane-Myers A, Cheung-Chau KW, Kwong-Fuk Tai A, Manfioletti G et al. The architectural transcription factor high mobility group I(Y) participates in photoreceptor-specific gene expression. Journal of Neuroscience. 2000 Oct 1;20(19):7317-7324.
Chau, K. Y. ; Munshi, N. ; Keane-Myers, A. ; Cheung-Chau, K. W. ; Kwong-Fuk Tai, A. ; Manfioletti, G. ; Dorey, C. K. ; Thanos, D. ; Zack, D. J. ; Ono, S. J. / The architectural transcription factor high mobility group I(Y) participates in photoreceptor-specific gene expression. In: Journal of Neuroscience. 2000 ; Vol. 20, No. 19. pp. 7317-7324.
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