A Conserved Insulator That Recruits CTCF and Cohesin Exists between the Closely Related but Divergently Regulated Interleukin-3 and Granulocyte-Macrophage Colony-Stimulating Factor Genes

Bowers, Sarion R.; Mirabella, Fabio; Calero-Nieto, Fernando J.; Valeaux, Stephanie; Hadjur, Suzana; Baxter, Euan W.; Merkenschlager, Matthias; Cockerill, Peter N.

doi:10.1128/mcb.01411-08

Cited by 27 publications

(30 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Reactivation was associated with the strength of the match to the CTCF consensus sequence, also consistent with a direct effect on CTCF binding ( Figure S3A). By classifying CTCF-binding sites by sequence similarity into three known binding modes (Bowers et al, 2009;Filippova et al, 1996;Nakahashi et al, 2013;Ohlsson et al, 2001;Rhee and Pugh, 2011), including engagement of zinc fingers 3-7 (core sites) and additional specific interactions by zinc fingers 8-10 (upstream and extended spacing sites), we found that core sites were reactivated 42% more frequently than upstream sites ( Figure S3B), supporting speculation that different modes of engagement of its 11 zinc fingers may confer functional selectivity (Ohlsson et al, 2010). …”

Section: Methylation Modulates the Ctcf-dna Binding Interface At Labisupporting

confidence: 58%

Role of DNA Methylation in Modulating Transcription Factor Occupancy

et al. 2015

View full text Add to dashboard Cite

Although DNA methylation is commonly invoked as a mechanism for transcriptional repression, the extent to which it actively silences transcription factor (TF) occupancy sites in vivo is unknown. To study the role of DNA methylation in the active modulation of TF binding, we quantified the effect of DNA methylation depletion on the genomic occupancy patterns of CTCF, an abundant TF with known methylation sensitivity that is capable of autonomous binding to its target sites in chromatin. Here, we show that the vast majority (>98.5%) of the tens of thousands of unoccupied, methylated CTCF recognition sequences remain unbound upon abrogation of DNA methylation. The small fraction of sites that show methylation-dependent binding in vivo are in turn characterized by highly variable CTCF occupancy across cell types. Our results suggest that DNA methylation is not a primary groundskeeper of genomic TF landscapes, but rather a specialized mechanism for stabilizing intrinsically labile sites.

show abstract

Section: Methylation Modulates the Ctcf-dna Binding Interface At Labisupporting

confidence: 58%

Role of DNA Methylation in Modulating Transcription Factor Occupancy

et al. 2015

View full text Add to dashboard Cite

show abstract

“…These genes reside within a 145 kb chromatin domain demarcated by two prominent binding sites for the insulator factor CTCF which may represent chromatin boundaries, as previously shown for a cluster of CTCF sites in the IL3/CSF2 locus (71). The Th2 cytokine gene locus is controlled by a single locus control region (LCR) which resides within the Rad50 gene between Il13 and Il5 (72, 73).…”

Section: Studies Of the Th2 Cytokine Gene Locus As A Model For Chromamentioning

confidence: 62%

T Cell Receptor and Cytokine Signaling Can Function at Different Stages to Establish and Maintain Transcriptional Memory and Enable T Helper Cell Differentiation

et al. 2017

Self Cite

View full text Add to dashboard Cite

Experienced T cells exhibit immunological memory via a rapid recall response, responding to restimulation much faster than naïve T cells. The formation of immunological memory starts during an initial slow response, when naïve T cells become transformed to proliferating T blast cells, and inducible immune response genes are reprogrammed as active chromatin domains. We demonstrated that these active domains are supported by thousands of priming elements which cooperate with inducible transcriptional enhancers to enable efficient responses to stimuli. At the conclusion of this response, a small proportion of these cells return to the quiescent state as long-term memory T cells. We proposed that priming elements can be established in a hit-and-run process dependent on the inducible factor AP-1, but then maintained by the constitutive factors RUNX1 and ETS-1. This priming mechanism may also function to render genes receptive to additional differentiation-inducing factors such as GATA3 and TBX21 that are encountered under polarizing conditions. The proliferation of recently activated T cells and the maintenance of immunological memory in quiescent memory T cells are also dependent on various cytokine signaling pathways upstream of AP-1. We suggest that immunological memory is established by T cell receptor signaling, but maintained by cytokine signaling.

show abstract

“…CTCF functions at transcriptional insulators that disrupt enhancer-promoter communication (Wallace and Felsenfeld, 2007). Recruitment of cohesin to CTCF binding sites may require interaction with CTCF (Rubio et al, 2008), and studies suggest that cohesin influences the activity of cis-regulatory elements that bind CTCF (Bowers et al, 2009; Hadjur et al, 2009). However, cohesin also binds several sites in the human genome independently of CTCF (Schmidt et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Positive regulation of c-Myc by cohesin is direct, and evolutionarily conserved

Rhodes

Bentley

et al. 2010

Developmental Biology

126

View full text Add to dashboard Cite

Contact between sister chromatids from S phase to anaphase depends on cohesin, a large multi-subunit protein complex. Mutations in sister chromatid cohesion proteins underlie the human developmental condition, Cornelia de Lange Syndrome. Roles for cohesin in regulating gene expression, sometimes in combination with CCCTC-binding factor (CTCF), have emerged. We analyzed zebrafish embryos null for cohesin subunit rad21 using microarrays to determine global effects of cohesin on gene expression during embryogenesis. This identified Rad21-associated gene networks that included myca (zebrafish c-myc), p53 and mdm2. In zebrafish, cohesin binds to the transcription start sites of p53 and mdm2, and depletion of either Rad21 or CTCF increased their transcription. In contrast, myca expression was strongly downregulated upon loss of Rad21 while depletion of CTCF had little effect. Depletion of Rad21 or the cohesin-loading factor Nipped-B in Drosophila cells also reduced expression of myc and Myc target genes. Cohesin bound the transcription start site plus an upstream predicted CTCF binding site at zebrafish myca. Binding and positive regulation of the c-Myc gene by cohesin is conserved through evolution, indicating this regulation is likely to be direct. The exact mechanism of regulation is unknown, but local changes in histone modification associated with transcription repression at the myca gene were observed in rad21 mutants.

show abstract

A Conserved Insulator That Recruits CTCF and Cohesin Exists between the Closely Related but Divergently Regulated Interleukin-3 and Granulocyte-Macrophage Colony-Stimulating Factor Genes

Cited by 27 publications

References 45 publications

Role of DNA Methylation in Modulating Transcription Factor Occupancy

Role of DNA Methylation in Modulating Transcription Factor Occupancy

T Cell Receptor and Cytokine Signaling Can Function at Different Stages to Establish and Maintain Transcriptional Memory and Enable T Helper Cell Differentiation

Positive regulation of c-Myc by cohesin is direct, and evolutionarily conserved

Contact Info

Product

Resources

About