The human β-globin locus control region can silence as well as activate gene expression

Yong Qing Feng, Renaud Warin, Taihao Li, Emmanuel Olivier, Arnaud Besse, Amanda Lobell, Haiqing Fu, Mei Lin Chii, Mirit I. Aladjem, Eric E. Bouhassira

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

Using recombinase-mediated cassette exchange to test multiple transgenes at the same site of integration, we demonstrate a novel chromatin context-dependent silencer activity of the β-globin locus control region (LCR). This silencer activity requires DNase I hypersensitive sites HS2 and HS3 but not HS4. After silencing, the silenced cassettes adopt a typical closed chromatin conformation (histone H3 and H4 deacetylation, histone H3-K4 methylation, DNA methylation, and replication in late S phase). In the absence of the LCR at the same site of integration, the chromatin remains decondensed. We demonstrate that the LCR is necessary but not sufficient to trigger these chromatin changes. We also provide evidence that this novel silencing activity is caused by transcriptional interference triggered by activation of transcription in the flanking sequences by the LCR.

Original languageEnglish (US)
Pages (from-to)3864-3874
Number of pages11
JournalMolecular and cellular biology
Volume25
Issue number10
DOIs
StatePublished - May 1 2005

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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