HMG I/Y regulates long-range enhancer-dependent transcription on DNA and chromatin by changes in DNA topology

Rajesh Bagga, Susan Michalowski, Rohit Sabnis, Jack D. Griffith, Beverly Emerson

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

The nature of nuclear structures that are required to confer transcriptional regulation by distal enhancers is unknown. We show that long-range enhancer-dependent β-globin transcription is achieved in vitro upon addition of the DNA architectural protein HMG I/Y to affinity-enriched holo RNA polymerase II complexes. In this system, HMG I/Y represses promoter activity in the absence of an associated enhancer and strongly activates transcription in the presence of a distal enhancer. Importantly, nucleosome formation is neither necessary for long-range enhancer regulation in vitro nor sufficient without the addition of HMG I/Y. Thus, the modulation of DNA structure by HMG I/Y is a critical regulator of long-range enhancer function on both DNA and chromatin-assembled genes. Electron microscopic analysis reveals that HMG I/Y binds cooperatively to preferred DNA sites to generate distinct looped structures in the presence or absence of the β-globin enhancer. The formation of DNA topologies that enable distal enhancers to strongly regulate gene expression is an intrinsic property of HMG I/Y and naked DNA.

Original languageEnglish (US)
Pages (from-to)2541-2550
Number of pages10
JournalNucleic acids research
Volume28
Issue number13
DOIs
StatePublished - Jul 1 2000
Externally publishedYes

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Chromatin
DNA
Globins
HMGA1a Protein
Nucleosomes
RNA Polymerase II
Electrons
Gene Expression
Genes
In Vitro Techniques

ASJC Scopus subject areas

  • Genetics

Cite this

HMG I/Y regulates long-range enhancer-dependent transcription on DNA and chromatin by changes in DNA topology. / Bagga, Rajesh; Michalowski, Susan; Sabnis, Rohit; Griffith, Jack D.; Emerson, Beverly.

In: Nucleic acids research, Vol. 28, No. 13, 01.07.2000, p. 2541-2550.

Research output: Contribution to journalArticle

Bagga, Rajesh ; Michalowski, Susan ; Sabnis, Rohit ; Griffith, Jack D. ; Emerson, Beverly. / HMG I/Y regulates long-range enhancer-dependent transcription on DNA and chromatin by changes in DNA topology. In: Nucleic acids research. 2000 ; Vol. 28, No. 13. pp. 2541-2550.
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