Tal1/SCL binding to pericentromeric DNA represses transcription

Jie Wen, Suming Huang, Svetlana D. Pack, Xiaobing Yu, Stephen J. Brandt, Constance Tom Noguchi

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Tal1/SCL is a basic helix-loop-helix transcription factor critical for normal hematopoiesis. To understand the mechanisms underlying transcriptional regulation by Tal1/SCL, we combined an in vitro DNA binding strategy and an in vivo chromatin immunoprecipitation analysis to search for Tal1/SCL target regions in K562 erythroleukemia cells. A 0.4-kb genomic DNA clone containing two Tal1/SCL binding E-boxes and GATA- and SATB1-binding motifs (EEGS) was identified that localized to the pericentromeric region with high homology to satellite 2 DNA. Pericentric DNA is related to heterochromatin and gene inactivation. We found that Tal1/SCL could complex with the histone H3 lysine 9 (H3K9)-specific methyltransferase Suv39H1. Binding of Tal1/SCL to EEGS chromatin correlated with hypermethylation of H3K9 and the association of heterochromatin protein HP1 to this region. In Rep4 reporter gene assays, EEGS affected repression in a manner dependent on the expression level of Tal1/SCL that was accompanied by increased H3K9 methylation in chromatin associated with EEGS and a linked promoter. A specific histone deacetylase inhibitor, trichostatin A, relieved Tal1/SCL-mediated repression by EEGS. In addition, SATB1 bound EEGS chromatin and promoted Tal1/SCL EEGS-dependent repression. We expand the list of potential interacting partners for Tal1/SCL by demonstrating direct associations of Tal1/SCL with SATB1 and with Suv39H1. These results reveal a novel mechanism of action for Tal1/SCL and implicate heterochromatin-like silencing via a cis-acting binding motif for transcriptional repression.

Original languageEnglish (US)
Pages (from-to)12956-12966
Number of pages11
JournalJournal of Biological Chemistry
Volume280
Issue number13
DOIs
StatePublished - Apr 1 2005

Fingerprint

Heterochromatin
Transcription
Chromatin
DNA
trichostatin A
Basic Helix-Loop-Helix Transcription Factors
Satellite DNA
Leukemia, Erythroblastic, Acute
Histone Deacetylase Inhibitors
K562 Cells
Genes
Chromatin Immunoprecipitation
Hematopoiesis
Methyltransferases
Gene Silencing
Reporter Genes
Histones
Methylation
Lysine
Clone Cells

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Wen, J., Huang, S., Pack, S. D., Yu, X., Brandt, S. J., & Noguchi, C. T. (2005). Tal1/SCL binding to pericentromeric DNA represses transcription. Journal of Biological Chemistry, 280(13), 12956-12966. https://doi.org/10.1074/jbc.M412721200
Wen, Jie ; Huang, Suming ; Pack, Svetlana D. ; Yu, Xiaobing ; Brandt, Stephen J. ; Noguchi, Constance Tom. / Tal1/SCL binding to pericentromeric DNA represses transcription. In: Journal of Biological Chemistry. 2005 ; Vol. 280, No. 13. pp. 12956-12966.
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Wen, J, Huang, S, Pack, SD, Yu, X, Brandt, SJ & Noguchi, CT 2005, 'Tal1/SCL binding to pericentromeric DNA represses transcription', Journal of Biological Chemistry, vol. 280, no. 13, pp. 12956-12966. https://doi.org/10.1074/jbc.M412721200

Tal1/SCL binding to pericentromeric DNA represses transcription. / Wen, Jie; Huang, Suming; Pack, Svetlana D.; Yu, Xiaobing; Brandt, Stephen J.; Noguchi, Constance Tom.

In: Journal of Biological Chemistry, Vol. 280, No. 13, 01.04.2005, p. 12956-12966.

Research output: Contribution to journalArticle

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AU - Wen, Jie

AU - Huang, Suming

AU - Pack, Svetlana D.

AU - Yu, Xiaobing

AU - Brandt, Stephen J.

AU - Noguchi, Constance Tom

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