Article

Cell type specificity of chromatin organization mediated by CTCF and cohesin.

Laboratory of Cellular and Developmental Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.81). 02/2010; 107(8):3651-6. DOI: 10.1073/pnas.0912087107
Source: PubMed

ABSTRACT CTCF sites are abundant in the genomes of diverse species but their function is enigmatic. We used chromosome conformation capture to determine long-range interactions among CTCF/cohesin sites over 2 Mb on human chromosome 11 encompassing the beta-globin locus and flanking olfactory receptor genes. Although CTCF occupies these sites in both erythroid K562 cells and fibroblast 293T cells, the long-range interaction frequencies among the sites are highly cell type specific, revealing a more densely clustered organization in the absence of globin gene activity. Both CTCF and cohesins are required for the cell-type-specific chromatin conformation. Furthermore, loss of the organizational loops in K562 cells through reduction of CTCF with shRNA results in acquisition of repressive histone marks in the globin locus and reduces globin gene expression whereas silent flanking olfactory receptor genes are unaffected. These results support a genome-wide role for CTCF/cohesin sites through loop formation that both influences transcription and contributes to cell-type-specific chromatin organization and function.

0 Bookmarks
 · 
77 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Enhancers are cis-regulatory elements that enable precise spatiotemporal patterns of gene expression during development and are notable for being able to function at large distances from their target genes. Such regulatory elements often bypass intervening genes and typically comprise binding sites for multiple transcription factors that can also be transcribed by RNA polymerase II (Pol II) to produce noncoding enhancer RNAs (eRNAs). Genome-wide analyses have revealed chromatin signatures of enhancers, such as the enrichment for monomethylation of histone H3 lysine 4 (H3K4me1) and the acetylation or methylation of histone H3 lysine 27 (H3K27). Enhancer signatures have been used to describe the transitions of these regulatory elements from inactive to primed and from activated to decommissioned states during development. New mutations of enhancer sequences and of the protein factors regulating enhancer function in human disease continue to be identified, contributing to a growing class of 'enhanceropathies'.
    Nature Structural & Molecular Biology 03/2014; 21(3):210-9. · 11.90 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The eukaryotic genome is organized in the three-dimensional nuclear space in a specific manner that is both a cause and a consequence of its function. This organization is partly established by a special class of architectural proteins, of which CCCTC-binding factor (CTCF) is the best characterized. Although CTCF has been assigned various roles that are often contradictory, new results now help to draw a unifying model to explain the many functions of this protein. CTCF creates boundaries between topologically associating domains in chromosomes and, within these domains, facilitates interactions between transcription regulatory sequences. Thus, CTCF links the architecture of the genome to its function.
    Nature Reviews Genetics 03/2014; · 41.06 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The structural maintenance of chromosomes (SMC) complexes are associated with transcriptional enhancers, promoters and insulators, where they contribute to the control of gene expression and genome structure. We review here recent insights into the interlinked roles of SMC complexes in gene expression and genome architecture. Among these, we note evidence that SMC complexes play important roles in the regulation of genes that control cell identity. We conclude by reviewing diseases associated with SMC mutations.
    Current opinion in genetics & development 05/2014; 25C:131-137. · 8.99 Impact Factor

Full-text

View
1 Download
Available from