Chromatin insulators: lessons from the fly

Gurudatta, B. V.; Corcés, Victor G.

doi:10.1093/bfgp/elp032

Cited by 52 publications

(51 citation statements)

References 35 publications

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“…Mouse α-H3S10ph (Millipore 05-806) at 1:4,000 binding proteins to target the accessory proteins to different regions of the genome. 55,56 The different subclasses of Drosophila insulators show distinct localization patterns with respect to gene features, suggesting different roles in nuclear biology. However, the different insulator subclasses also cluster at specific genomic locations, where they synergize to create stronger insulators.…”

Section: Methodsmentioning

confidence: 99%

Dynamic changes in the genomic localization of DNA replication-related element binding factor during the cell cycle

et al. 2013

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Section: Methodsmentioning

confidence: 99%

Dynamic changes in the genomic localization of DNA replication-related element binding factor during the cell cycle

et al. 2013

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“…Simple biological possibilities are that some Twist occupancy is not associated with any regulatory activity; that the module's regulatory activity is to silence or to insulate, rather than to enhance; that the module is bound but is not active at this time in development (for review, see Levine and Tjian 2003;Arnosti and Kulkarni 2005;Gurudatta and Corces 2009;Cao et al 2010). There are precedents for all these possibilities, although not all have been explicitly shown for Twist.…”

Section: In Vivo Chip Data For Twist At Binding Site Resolutionmentioning

confidence: 99%

High resolution mapping of Twist to DNA in Drosophila embryos: Efficient functional analysis and evolutionary conservation

Özdemir¹,

Fisher-Aylor²,

Pepke³

et al. 2011

Genome Res.

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Cis-regulatory modules (CRMs) function by binding sequence specific transcription factors, but the relationship between in vivo physical binding and the regulatory capacity of factor-bound DNA elements remains uncertain. We investigate this relationship for the well-studied Twist factor in Drosophila melanogaster embryos by analyzing genome-wide factor occupancy and testing the functional significance of Twist occupied regions and motifs within regions. Twist ChIP-seq data efficiently identified previously studied Twist-dependent CRMs and robustly predicted new CRM activity in transgenesis, with newly identified Twist-occupied regions supporting diverse spatiotemporal patterns (>74% positive, n = 31). Some, but not all, candidate CRMs require Twist for proper expression in the embryo. The Twist motifs most favored in genome ChIP data (in vivo) differed from those most favored by Systematic Evolution of Ligands by EXponential enrichment (SELEX) (in vitro). Furthermore, the majority of ChIP-seq signals could be parsimoniously explained by a CABVTG motif located within 50 bp of the ChIP summit and, of these, CACATG was most prevalent. Mutagenesis experiments demonstrated that different Twist E-box motif types are not fully interchangeable, suggesting that the ChIP-derived consensus (CABVTG) includes sites having distinct regulatory outputs. Further analysis of position, frequency of occurrence, and sequence conservation revealed significant enrichment and conservation of CABVTG E-box motifs near Twist ChIP-seq signal summits, preferential conservation of 6150 bp surrounding Twist occupied summits, and enrichment of GA-and CA-repeat sequences near Twist occupied summits. Our results show that high resolution in vivo occupancy data can be used to drive efficient discovery and dissection of global and local cis-regulatory logic.

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“…Two observations suggest that the fertility and insulator functions of Su(Hw) are independent. First, a loss of Su(Hw) occupancy at ~60% of genomic SBSs has no effect on fertility (Soshnev et al, 2012), an unexpected finding for an insulator-dependent function that has been linked to the formation of physical chromatin domains important for transcriptional regulation (Gurudatta and Corces, 2009;Yang and Corces, 2011;Hou et al, 2012). Second, fertility is unaffected by loss of CP190 and Mod67.2 (Chodagam et al, 2005;Baxley et al, 2011), two partners that are required for Su(Hw) insulator function.…”

Section: Introductionmentioning

confidence: 99%

The insulator protein Suppressor of Hairy-wing is an essential transcriptional repressor in theDrosophilaovary

et al. 2013

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SUMMARYSuppressor of Hairy-wing [Su(Hw)] is a DNA-binding factor required for gypsy insulator function and female germline development in Drosophila. The insulator function of the gypsy retrotransposon depends on Su(Hw) binding to clustered Su(Hw) binding sites (SBSs) and recruitment of the insulator proteins Centrosomal Protein 190 kD (CP190) and Modifier of mdg4 67.2 kD (Mod67.2). By contrast, the Su(Hw) germline function involves binding to non-clustered SBSs and does not require CP190 or Mod67.2. Here, we identify Su(Hw) target genes, using genome-wide analyses in the ovary to uncover genes with an ovary-bound SBS that are misregulated upon Su(Hw) loss. Most Su(Hw) target genes demonstrate enriched expression in the wild-type CNS. Loss of Su(Hw) leads to increased expression of these CNS-enriched target genes in the ovary and other tissues, suggesting that Su(Hw) is a repressor of neural genes in non-neural tissues. Among the Su(Hw) target genes is RNA-binding protein 9 (Rbp9), a member of the ELAV/Hu gene family. Su(Hw) regulation of Rbp9 appears to be insulator independent, as Rbp9 expression is unchanged in a genetic background that compromises the functions of the CP190 and Mod67.2 insulator proteins, even though both localize to Rbp9 SBSs.

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Chromatin insulators: lessons from the fly

Cited by 52 publications

References 35 publications

Dynamic changes in the genomic localization of DNA replication-related element binding factor during the cell cycle

Dynamic changes in the genomic localization of DNA replication-related element binding factor during the cell cycle

High resolution mapping of Twist to DNA in Drosophila embryos: Efficient functional analysis and evolutionary conservation

The insulator protein Suppressor of Hairy-wing is an essential transcriptional repressor in theDrosophilaovary

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