The Enhancer-Blocking Activity of the Fab-7 Boundary From the Drosophila Bithorax Complex Requires GAGA-Factor-Binding Sites

Schweinsberg, Susan E.; Hagstrom, Kirsten; Gohl, Daryl M.; Schedl, Paul; Kumar, Ram P.; Mishra, Rakesh K.; Karch, François

doi:10.1534/genetics.104.029561

Cited by 102 publications

(112 citation statements)

References 71 publications

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“…S3a), confirming that GATA by itself is sufficient for the boundary activity. It should also be noted that the enhancer blocker activity is not a property of any repetitive element but rather is an attribute of GATA SSR exclusively, as earlier reports from our lab have shown that GAGAG repeat fails to act as a boundary despite GAGAG motif having the ability to recruit GAGA boundary factor 25 .…”

Section: Gata Ssr Functions As Enhancer Blocker In Human Cellsmentioning

confidence: 77%

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: Gata Ssr Functions As Enhancer Blocker In Human Cellsmentioning

confidence: 77%

GATA simple sequence repeats function as enhancer blocker boundaries

et al. 2013

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“…Moreover, the GAGA-binding sites in HS1 are important for boundary function. In previous studies, we found that the enhancer blocking activity of the minimal 1.2 kb boundary is compromised in both the embryo and adult when GAGA sites 1-5 are mutated (Schweinsberg et al, 2004). Although this finding indicates that GAGA (or another protein that recognizes the GAGA consensus) is required for Fab-7 boundary activity throughout development, the GAGA sites are not functionally equivalent.…”

Section: Introductionmentioning

confidence: 77%

Developmental modulation ofFab-7boundary function

Schweinsberg

Schedl

2004

Development

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The Fab-7 boundary functions to ensure the autonomous activity of the iab-6 and iab-7 cis-regulatory domains in the Drosophila Bithorax Complex from early embryogenesis through to the adult stage. Although Fab-7 is required only for the proper development of a single posterior parasegment, it is active in all tissues and stages of development that have been examined. In this respect, Fab-7resembles conventional constitutive boundaries in flies and other eukaryotes that act through ubiquitous cis-elements and trans-acting factors. Surprisingly, however, we find that the constitutive activity of Fab-7 is generated by combining sub-elements with developmentally restricted boundary function. We provide in vivo evidence that the Fab-7 boundary contains separable regions that function at different stages of development. These findings suggest that the units (domains) of genetic regulation that boundaries delimit can expand or contract by switching insulator function off or on in a temporally regulated fashion.

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“…For example, such a role has been suggested for GAF in the case of Fab-7 and SF1 insulators, which have many GAF binding sites. 45,46 Thus, further studies are necessary for elucidating the role of BTB domains of the ttk group in longdistance interactions and their other possible activities in transcriptional regulation.…”

Section: Discussionmentioning

confidence: 99%

Drosophila BTB/POZ Domains of “ttk Group” Can Form Multimers and Selectively Interact with Each Other

Bonchuk

Denisov

Georgiev

et al. 2011

Journal of Molecular Biology

105

109

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Edited by M. GottesmanKeywords: GAGA; BTB domain; Mod(mdg4); CP190; chromatin insulatorThe BTB (bric-a-brac, tramtrack and broad complex)/POZ (poxvirus and zinc finger) domain is a conserved protein-protein interaction motif contained in a variety of transcription factors involved in development, chromatin remodeling, insulator activity, and carcinogenesis. All wellstudied mammalian BTB domains form obligate homodimers and, rarely, tetramers. Only the BTB domain of the Drosophila GAGA factor (GAF) has been shown to exist as higher-order multimers. The BTB domain of GAF belongs to the "ttk group" that contains several highly conserved sequences not found in other BTB domains. Here, we have shown by size-exclusion chromatography, chemical cross-linking, and nondenaturing PAGE that four additional BTB domains of the ttk group-Batman, Mod(mdg4), Pipsqueak, and Tramtrack-can form multimers, like GAF. Interestingly, the BTB domains of GAF and Batman have formed a wide range of complexes and interacted in the yeast two-hybrid assay with other BTB domains tested. In contrast, the BTB domains of Mod(mdg4), Pipsqueak, and Tramtrack have formed stable high-order multimer complexes and failed to interact with each other. The BTB domain of Drosophila CP190 protein does not belong to the ttk group. This BTB domain has formed stable dimers and has not interacted with domains of the ttk group. Previously, it was suggested that GAF oligomerization into higher-order complexes facilitates long-range activation by providing a protein bridge between an enhancer and a promoter. Unexpectedly, experiments in the Drosophila model system have not supported the role of GAF in organization of longdistance interaction between the yeast GAL4 activator and the white promoter.© 2011 Elsevier Ltd. All rights reserved. IntroductionThe BTB (bric-a-brac, tramtrack and broad complex) domain [also known as the POZ (poxvirus and zinc finger) domain] is a versatile protein-protein interaction motif that participates in a wide range of cellular functions, including transcription regulation (for review, see Ref. 1 ). Transcription factors with a BTB domain at the N-terminus comprise a large important class of molecules involved in development and carcinogenesis. As shown in crystallographic studies,

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The Enhancer-Blocking Activity of the Fab-7 Boundary From the Drosophila Bithorax Complex Requires GAGA-Factor-Binding Sites

Cited by 102 publications

References 71 publications

GATA simple sequence repeats function as enhancer blocker boundaries

GATA simple sequence repeats function as enhancer blocker boundaries

Developmental modulation ofFab-7boundary function

Drosophila BTB/POZ Domains of “ttk Group” Can Form Multimers and Selectively Interact with Each Other

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