CTCF is conserved from
            <i>Drosophila</i>
            to humans and confers enhancer blocking of the
            <i>Fab‐8</i>
            insulator

Moon, Heehyul; Filippova, Galina N.; Loukinov, Dmitry; Pugacheva, Elena M.; Chen, Qi; Smith, Sheryl T.; Munhall, Adam C.; Grewe, Britta; Bartkuhn, Marek; Arnold, Rüdiger; Burke, Les J.; Renkawitz‐Pohl, Renate; Ohlsson, Rolf; Zhou, Jumin; Renkawitz, Rainer; Lobanenkov, Victor

doi:10.1038/sj.embor.7400334

Cited by 223 publications

(267 citation statements)

References 30 publications

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“…First, CTCF-binding sites should exist between individual genes of a Hox cluster. This property is well documented in both vertebrates and Drosophila (10,28,40,43,55,56), suggesting that it existed in the ancestor of protostomes and deuterostomes. Second, owing to the stability of the proposed kernel, one should find signs of conservation at least at some CTCF-binding sites.…”

Section: Conservation Of Ctcf Sites In Vertebrate and Drosophila Hox mentioning

confidence: 95%

“…In D. melanogaster, CTCF confers insulator activity to the Fab-6 and Fab-8 chromatin boundaries within the Bithorax Hox complex (BX-C) (10,41). With the exception of Fab-7, all known and postulated boundaries within BX-C bind CTCF in vivo (28 transformations (31,42).…”

Section: Conservation Of Ctcf Sites In Vertebrate and Drosophila Hox mentioning

confidence: 99%

“…The presence of CTCF in vertebrates (11,(18)(19)(20), flies (10,21), and some nematodes (22) suggests that all protostomes and deuterostomes might possess this 11-ZF protein. To investigate this possibility, we searched in public databases for CTCF candidates and determined their orthology to CTCF in a phylogenetic analysis.…”

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confidence: 99%

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The chromatin insulator CTCF and the emergence of metazoan diversity

Heger

Marin²,

Bartkuhn

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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172

173

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The great majority of metazoans belong to bilaterian phyla. They diversified during a short interval in Earth's history known as the Cambrian explosion, ∼540 million years ago. However, the genetic basis of these events is poorly understood. Here we argue that the vertebrate genome organizer CTCF (CCCTC-binding factor) played an important role for the evolution of bilaterian animals. We provide evidence that the CTCF protein and a genome-wide abundance of CTCF-specific binding motifs are unique to bilaterian phyla, but absent in other eukaryotes. We demonstrate that CTCF-binding sites within vertebrate and Drosophila Hox gene clusters have been maintained for several hundred million years, suggesting an ancient origin of the previously known interaction between Hox gene regulation and CTCF. In addition, a close correlation between the presence of CTCF and Hox gene clusters throughout the animal kingdom suggests conservation of the Hox-CTCF link across the Bilateria. On the basis of these findings, we propose the existence of a Hox-CTCF kernel as principal organizer of bilaterian body plans. Such a kernel could explain (i) the formation of Hox clusters in Bilateria, (ii) the diversity of bilaterian body plans, and (iii) the uniqueness and time of onset of the Cambrian explosion.

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Section: Conservation Of Ctcf Sites In Vertebrate and Drosophila Hox mentioning

confidence: 95%

Section: Conservation Of Ctcf Sites In Vertebrate and Drosophila Hox mentioning

confidence: 99%

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The chromatin insulator CTCF and the emergence of metazoan diversity

Heger

Marin²,

Bartkuhn

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

172

173

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“…[4][5][6] Furthermore, both context-dependent activity and ubiquitous global distribution are conserved throughout vertebrates and insects. [7][8][9][10][11][12][13] Recent studies of CTCF suggest that the mechanism of this multifunctional transcriptional regulation may involve higher order chromatin structure.…”

Section: Introductionmentioning

confidence: 99%

CTCF terminal segments are unstructured

Martinez

Miranda

2010

Protein Science

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The human CCCTC-binding factor, CTCF, organizes and regulates transcription of the genome by colocalizing distant DNA elements on the same and even different chromosomes. This protein consists of 11 zinc fingers flanked by polypeptide segments of unknown structure and function. We purified recombinant terminal fragments and observed that both are extended, monomeric, and predominantly consist of unordered content. We thus speculate that the role of the terminal extensions, and perhaps all of CTCF, is to act as a scaffold for the assembly of other proteins on a specific binding site.

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“…Recent studies have revealed an abundance of putative insulator elements bound by the enhancer-blocking protein CTCF in mammalian genomes, and predicted a similar number of binding sites in Tetraodon (Kim et al 2007;Xie et al 2007). Human CTCF is functionally conserved in Drosophila, where several other enhancer-blocking proteins also are known (Moon et al 2005). It will be interesting to see whether insulator elements are present at the borders of vertebrate and Drosophila GRBs.…”

Section: Responsiveness Of Genes To Long-range Enhancersmentioning

confidence: 99%

Genomic regulatory blocks underlie extensive microsynteny conservation in insects

Engström¹,

Sui²,

Drivenes³

et al. 2007

Genome Res.

191

208

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Insect genomes contain larger blocks of conserved gene order (microsynteny) than would be expected under a random breakage model of chromosome evolution. We present evidence that microsynteny has been retained to keep large arrays of highly conserved noncoding elements (HCNEs) intact. These arrays span key developmental regulatory genes, forming genomic regulatory blocks (GRBs). We recently described GRBs in vertebrates, where most HCNEs function as enhancers and HCNE arrays specify complex expression programs of their target genes. Here we present a comparison of five Drosophila genomes showing that HCNE density peaks centrally in large synteny blocks containing multiple genes. Besides developmental regulators that are likely targets of HCNE enhancers, HCNE arrays often span unrelated neighboring genes. We describe differences in core promoters between the target genes and the unrelated genes that offer an explanation for the differences in their responsiveness to enhancers. We show examples of a striking correspondence between boundaries of synteny blocks, HCNE arrays, and Polycomb binding regions, confirming that the synteny blocks correspond to regulatory domains. Although few noncoding elements are highly conserved between Drosophila and the malaria mosquito Anopheles gambiae, we find that A. gambiae regions orthologous to Drosophila GRBs contain an equivalent distribution of noncoding elements highly conserved in the yellow fever mosquito Aëdes aegypti and coincide with regions of ancient microsynteny between Drosophila and mosquitoes. The structural and functional equivalence between insect and vertebrate GRBs marks them as an ancient feature of metazoan genomes and as a key to future studies of development and gene regulation.

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CTCF is conserved from Drosophila to humans and confers enhancer blocking of the Fab‐8 insulator

Cited by 223 publications

References 30 publications

The chromatin insulator CTCF and the emergence of metazoan diversity

The chromatin insulator CTCF and the emergence of metazoan diversity

CTCF terminal segments are unstructured

Genomic regulatory blocks underlie extensive microsynteny conservation in insects

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