Fab-7 functions as a chromatin domain boundary to ensure proper segment specification by the Drosophila bithorax complex.

Hagstrom, Kirsten; Müller, Martin; Schedl, Paul

doi:10.1101/gad.10.24.3202

Cited by 226 publications

(237 citation statements)

References 47 publications

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“…For the enhancer blocker assay in human cell line, the XhoI fragments from LML were cloned into the modified pJC54 vector whereas for the repressor assay the fragments were amplified and cloned into NdeI site upstream to the enhancer. For Drosophila transgenic constructs, XhoI fragments from LML were inserted at XhoI site of the ftzEN:hsp70/lacZ (pCfhL) vector 23 (Fig. 2).…”

Section: Methodsmentioning

confidence: 99%

“…2a) 23 . GE5 (394 bp), GE7 (389 bp) and GE10 (930 bp) from the human Y chromosome ( Supplementary Fig.…”

Section: Gata Ssr Functions As Enhancer Blocker In Human Cellsmentioning

confidence: 99%

“…S1) were tested for boundary activity in this assay. We compared our results with the 'vector' control line containing no test DNA and blocker control line of 'Su(Hw) 5 ' (355 bp) as test fragment 23 . Genetic tools available in Drosophila enabled us to flip-out the test fragments from the transgenes using Cre recombinase-expressing fly and compare reporter activity in presence and absence of the test fragment while keeping the genomic context unchanged (Fig.…”

Section: Gata Ssr Functions As Enhancer Blocker In Human Cellsmentioning

confidence: 99%

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GATA simple sequence repeats function as enhancer blocker boundaries

et al. 2013

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Simple sequence repeats (SSRs) account for B3% of the human genome, but their functional significance still remains unclear. One of the prominent SSRs the GATA tetranucleotide repeat has preferentially accumulated in complex organisms. GATA repeats are particularly enriched on the human Y chromosome, and their non-random distribution and exclusive association with genes expressed during early development indicate their role in coordinated gene regulation. Here we show that GATA repeats have enhancer blocker activity in Drosophila and human cells. This enhancer blocker activity is seen in transgenic as well as native context of the enhancers at various developmental stages. These findings ascribe functional significance to SSRs and offer an explanation as to why SSRs, especially GATA, may have accumulated in complex organisms.

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Section: Methodsmentioning

confidence: 99%

“…2a) 23 . GE5 (394 bp), GE7 (389 bp) and GE10 (930 bp) from the human Y chromosome ( Supplementary Fig.…”

Section: Gata Ssr Functions As Enhancer Blocker In Human Cellsmentioning

confidence: 99%

Section: Gata Ssr Functions As Enhancer Blocker In Human Cellsmentioning

confidence: 99%

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GATA simple sequence repeats function as enhancer blocker boundaries

et al. 2013

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“…The phrase denotes (nonexclusively): alternative looping that brings into action a given CRM under given circumstances and other CRMs under other circumstances; insulators that prevent more proximal CRMs from interacting with a BTA while permitting more distal ones to so interact (e.g., refs. [22][23][24]; insulators that, in certain developmental circumstances, transfer a given CRM to an inaccessible or sequestered chromatin domain (e.g., see refs. 25 and 26); and distant locus activators that, if bound by the factors for which they contain target sites permit more proximal CRMs to be active, probably by means of loop formation with them (27)(28)(29).…”

Section: External Functions (E Operators)mentioning

confidence: 99%

Logic functions of the genomic cis-regulatory code

Istrail

Davidson

2005

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

157

106

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cis-regulatory modules that control developmental gene expression process the regulatory inputs provided by the transcription factors for which they contain specific target sites. A prominent class of cis-regulatory processing functions can be modeled as logic operations. Many of these are combinatorial because they are mediated by multiple sites, although others are unitary. In this work, we illustrate the repertoire of cis-regulatory logic operations, as an approach toward a functional interpretation of the genomic regulatory code.T he differential control of gene expression during development depends primarily on transcription factor interactions with cis-regulatory modules (CRMs) that may be located upstream, downstream, or in the introns of a gene. The potential regulatory functions encoded in the DNA sequence of these modular control units are specified by the combinations of transcription factor target sites they contain, and, typically, a CRM will include sites for four to eight different interactions (1, 2). In the last analysis, it may be said that we will understand the genomic regulatory code only when we can interpret its functional significance by inspection, because it has been possible for decades to recognize protein coding sequence. However, at present, we cannot even recognize many cis-regulatory target sites; nor, perhaps more importantly, can we specify predictively, or, in some cases, even properly name, the elemental functions mediated by the individual sites within a CRM. Here, we take a step toward analysis of the repertoire of elemental cis-regulatory functions.For a developmentally expressed gene, regulatory control always depends in part on transcription factors presented variably in embryonic time and space. In the following, we use the term "driver" for such factors. These drivers provide spatial and temporal inputs (positive and negative) reflected in the regulatory output of the relevant CRM and in the resulting pattern of gene expression. However, target sites for driver inputs (3) may often account for only a minority of specific CRM target sites. Furthermore, the regulatory outputs of a CRM never exactly equal any of its inputs. This finding can be perceived explicitly when the inputs and outputs are hooked together in a gene regulatory network (2, 4-6). Instead, the CRM processes the driver inputs in a variety of complex ways, depending on its genomic design and, to some extent, on its genomic environs. We find that there is a class of fundamental processing functions mediated by specific CRM target sites and combinations of sites that have the behavior of logic operations, and it is on these sites that we focus herein. Initial Insights from endo16Endo16 is a developmentally regulated gene of the sea urchin embryo expressed in endodermal territory. In respect to its genomic regulatory code, endo16 may be the best understood of any developmentally active gene. The functional significance of every detectable target site in the two key CRMs of this gene was determined by mutation...

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“…Genetic, transgenic, and molecular studies have identified a number of classes of distinct cis-regulatory elements within the iab regions capable of directing abdA and AbdB expression. Insulator DNAs have been identified at the boundaries of the iab8-iab7 domains (Frontabdominal-8, Fab8) (4), iab7-iab6 domains (Fab7) (5)(6)(7)(8)(9)(10), and iab5-iab4 domains (Miscadastral pigmentation, Mcp) ( Fig. 1 A) (7,11).…”

Section: E Xpression Of the Abdominal-a (Abda) And Abdominal-b (Abdb)mentioning

confidence: 99%

Transcription defines the embryonic domains of cis-regulatory activity at the Drosophila bithorax complex

Drewell

Bae

Burr

et al. 2002

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

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The extensive infraabdominal (iab) region contains a number of cis-regulatory elements, including enhancers, silencers, and insulators responsible for directing the developmental expression of the abdominal-A and Abdominal-B homeotic genes at the Drosophila bithorax complex. It is unclear how these regulatory elements are primed for activity early in embryogenesis, but the 100-kb intergenic region is subject to a complex transcriptional program. Here, we use molecular and genetic methods to examine the functional activity of the RNAs produced from this region and their role in cis regulation. We show that a subset of these transcripts demonstrates a distinct pattern of cellular localization. Furthermore, the transcripts from each iab region are discrete and the transcripts do not spread across the insulator elements that delineate the iab regions. In embryos carrying a Mcp deletion, the intergenic transcription pattern is disrupted in the iab4 region and the fourth abdominal segment is transformed into the fifth. We propose that intergenic transcription is required early in embryogenesis to initiate the activation of the Drosophila bithorax complex and define the domains of activity for the iab cis-regulatory elements. We also discuss a possible mechanism by which this may occur.

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Fab-7 functions as a chromatin domain boundary to ensure proper segment specification by the Drosophila bithorax complex.

Cited by 226 publications

References 47 publications

GATA simple sequence repeats function as enhancer blocker boundaries

GATA simple sequence repeats function as enhancer blocker boundaries

Logic functions of the genomic cis-regulatory code

Transcription defines the embryonic domains of cis-regulatory activity at the Drosophila bithorax complex

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