Trends in Genetics
Anything else but GAGA: a nonhistone protein complex reshapes chromatin structure
Section snippets
Activation
During animal development, cellular identity and proper realization of the body plan depend on positional information provided by the expression patterns of the homeotic or Hox genes. The epigenetic maintenance of these patterns through mitotic cell divisions is believed to involve stable modifications of chromatin structure. Genetic screens in Drosophila have identified two groups of proteins that contribute to these modifications: the trithorax group (trxG) proteins, required for the
GAF cooperates with other chromatin remodeling activities
The primary effect of GAF binding in both gene activation and silencing seems to be the creation of nucleosome-free regions. Particularly well-documented are GAF-induced nucleosome rearrangements for the hsp26 and hsp70 genes, which respond to GAF by transcriptional activation 5, 11, 12. However, nucleosome-free regions that coincide with essential GAGA elements have also been found in the iab-7 and MCP silencer elements 20, 23, 38.
Nucleosome movement is an energy-dependent process, but no
Pipsqueak and Batman go GAGA: GAF as part of a heteromeric protein complex
Chromatin reorganization by GAF does not only play a role in transcription but is also required for the proper execution of mitosis 45, 46. The role of GAGA elements in the maintenance of human small nuclear (sn)RNA gene arrays [47] prompts speculations that GAF could also be involved in DNA recombination. How would a single DNA-binding protein be able to support such a broad spectrum of functions, including functions that are mutually exclusive, such as the activation and silencing of
Chromatin reorganization by GAF-containing protein complexes
Does GBP, as the basic GAGA-binding complex, displace nucleosomes to create a higher-order chromatin architecture? Natural target elements of GAF usually contain multiple variably spaced GAGA sites 4, 53, and a single complex formed by recombinant GAF in vitro can bind in a cooperative manner to sites scattered over a 200-bp stretch of DNA 53, 54. At the same time, BTB-mediated multimerization represses the binding to isolated GAGA sites and thus seems to be crucial for the recognition of
Specificity of GAF action: promoter context and promiscuous interactions
An obvious yet insufficiently explored possibility is that regulatory structures formed by GBP are locally modified through interactions with other BTB proteins. Interestingly, a recent study suggests that such interactions indeed contribute to the regulation of gene expression in vivo [58]. The BTB domain of Tramtrack (Ttk) binds to the GAF BTB domain in vitro [55], and in transient transfection experiments Ttk inhibits the GAF-dependent activation of the stripe 2 enhancer of the eve gene,
Concluding remarks
The existence of a GAGA-binding core complex consisting of GAF, Psq and Ban will have to be confirmed by biochemical purification of the complex from nuclear extracts. The availability of purified material will provide information about the stoichiometry and additional components of this complex. This in turn might help to address some of the outstanding questions that surround GBP function. For example, how do GBP complexes contribute to the formation of chromatin boundaries, and what do the
Acknowledgements
I apologize to all colleagues whose work is not or only indirectly cited because of space restrictions.
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Role of vertebrate GAGA associated factor (vGAF) in early development of zebrafish
2021, Cells and DevelopmentCitation Excerpt :This partial rescue confirmed that the ectopic expression of HoxD4 gene was due to depletion of GAF. In Drosophila, GAF is shown to be a key regulatory factor required for regulation of Hox gene expression(Bhat et al., 1996; Biggin and Tjian, 1988; Farkas et al., 1994; Lehmann, 2004; Mishra et al., 2001; Ohtsuki and Levine, 1998; Sabarinadh et al., 2003; Schweinsberg et al., 2004). Previous studies show that many GAF binding sites are present in number of intergenic regions of Hox clusters and several other cis-regulatory elements that are highly conserved within vertebrates (Kim et al., 2005; Min, 1998; Vasanthi et al., 2010; Woo et al., 2010).
The Growth arrest specific 1 (GAS1) gene is transcriptionally regulated by NeuroD1 via two distal E-boxes
2018, Experimental Cell ResearchCitation Excerpt :Intriguingly, an internal deletion in the promoter (pAE construct) blocked the response to all proneural factors, however, this deletion did not compromise the distal E boxes that potentially mediate this effect (Fig. 4E and F). Instead, the lost fragment of the promoter contains a long GAGA repeat (172 bp length) which has been associated with an especial chromatin structure essential for the interaction of distal and proximal elements during transcription [60] (see Discussion). Nevertheless, the specificity of the transcription factors was evident because the proximal E-box in the Gas1 promoter (the Mash1 binding motif) was intact in all deletions, but it was unable to mediate the responses exhibited when NeuroD1 or NeuroD2 were overexpressed.
Cooperative Recruitment of Polycomb Complexes by Polycomb Response Elements
2017, Polycomb Group ProteinsPolymorphic core promoter GA-repeats alter gene expression of the early embryonic developmental genes
2013, GeneCitation Excerpt :GA-repeats are a common class of core promoter STRs. Promoter sequences that include at least two GA-elements are necessary for nucleosome displacement when GAGA is competing directly with the nucleosome assembly reaction, and sequences including three to four elements are required for the disruption of a preassembled nucleosome (Lehmann, 2004; Melnikova et al., 2004; Oh et al., 2013; Tsukiyama et al., 1994). In all the reported promoters with GAGA-binding elements, the length of this binding site is limited to up to eight nucleotides (Brasset and Vaury, 2005).
GAGA factor repression of transcription is a rare event but the negative regulation of trl is conserved in drosophila species
2013, Biochimica et Biophysica Acta - Gene Regulatory Mechanisms