UMMS Affiliation

Program in Gene Function and Expression; Department of Biochemistry and Molecular Pharmacology

Publication Date

8-15-2006

Document Type

Article

Subjects

Adult; Biological Assay; Cell Line; Chromatin; Chromatin Immunoprecipitation; Fragile X Mental Retardation Protein; Gene Expression Regulation; Histones; Humans; Male; *Nucleic Acid Conformation; *Promoter Regions (Genetics)

Disciplines

Genetics and Genomics | Life Sciences | Medicine and Health Sciences

Abstract

We have analyzed the effects of gene activation on chromatin conformation throughout an approximately 170-kb region comprising the human fragile X locus, which includes a single expressed gene, FMR1 (fragile X mental retardation 1). We have applied three approaches: (i) chromosome conformation capture, which assesses relative interaction frequencies of chromatin segments; (ii) an extension of this approach that identifies domains whose conformation differs from the average, which we developed and named chromosome conformation profiling; and (iii) ChIP analysis of histone modifications. We find that, in normal cells where FMR1 is active, the FMR1 promoter is at the center of a large ( approximately 50 kb) domain of reduced intersegment interactions. In contrast, in fragile X cells where FMR1 is inactive, chromatin conformation is uniform across the entire region. We also find that histone modifications that are characteristic of active genes occur tightly localized around the FMR1 promoter in normal cells and are absent in fragile X cells. Therefore, the expression-correlated change in conformation affects a significantly larger domain than that marked by histone modifications. Domain-wide changes in interaction probability could reflect increased chromatin expansion and may also be related to an altered spatial disposition that results in increased intermingling with unrelated loci. The described approaches are widely applicable to the study of conformational changes of any locus of interest.

Comments

Citation: Proc Natl Acad Sci U S A. 2006 Aug 15;103(33):12463-8. Epub 2006 Aug 4. Link to article on publisher's site

© 2006 by The National Academy of Sciences of the USA

Publisher PDF posted as allowed by the publisher's author rights policy at http://www.pnas.org/site/misc/authorfaq.shtml.

Related Resources

Link to Article in PubMed

Journal/Book/Conference Title

Proceedings of the National Academy of Sciences of the United States of America

PubMed ID

16891414

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