Work

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

Year: 2000

Type: article

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 beta-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 beta-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.

Source: Nucleic Acids Research

DOI: 10.1093/nar/28.13.2541

Authors: R. Bagga, S. Michalowski, R. Sabnis, J. D. Griffith, B. M. Emerson

Institutions: Salk Institute for Biological Studies, University of North Carolina at Chapel Hill

Language: English

Topic: Genomics and Chromatin Dynamics

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: green

Funders: National Institutes of Health, National Cancer Institute, National Institute of General Medical Sciences

Awards: G2774293502, DNA-Protein Interactions at the Replication Fork, Integrated Training in Cancer Model Systems, G7410112167, Specificity of Mammalian SWI/SNF Remodeling Complexes