Sequence-specific transcriptional antirepression of the Drosophila Krüppel gene by the GAGA factor.

MeCP2 is an abundant mammalian protein that binds to methylated CpG. We have found that native and recombinant MeCP2 repress transcription in vitro from methylated promoters but do not repress nonmethylated promoters. Repression is nonlinearly dependent on the local density of methylation, becoming significant at the density found in bulk vertebrate genomic DNA. Transient transfection using fusions with the GAL4 DNA binding domain identified a region of MeCP2 that is capable of long-range repression in vivo. Moreover, MeCP2 is able to displace histone H1 from preassembled chromatin that contains methyl-CpG. These properties, together with the abundance of MeCP2 and the high frequency of its 2 bp binding site, suggest a role as a global transcriptional repressor in vertebrate genomes.

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“…and HindIII digestion of pG5E4T (Lin et al, 1988;Kerrigan et al, is due to their protection by bound MeCP2.…”

Section: Influence Of Methyl-cpg Density On Repressionmentioning

confidence: 99%

MeCP2 Is a Transcriptional Repressor with Abundant Binding Sites in Genomic Chromatin

Nan

Campoy

Bird

1997

Cell

1,153

881

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“…The GAGA factor may play an indirect role in restraining elongation of the polymerase through chromatin remodeling. Indeed, the GAGA factor can mediate anti-repression of transcription on chromatin templates (42,43), and is involved in remodeling the chromatin around both the hsp70 and the hsp26 promoters (44,45). Alternatively, the GAGA factor may play a direct role, perhaps by anchoring the RNA polymerase downstream of the promoter.…”

Section: What Is the Role Of Fbi-1?mentioning

confidence: 99%

“…BCL-6 and PLZF have been shown to associate with the co-repressor SMRT (silencing mediator of retinoid and thyroid receptor) (36) and may, therefore, be involved in chromatin remodeling by recruiting a histone deacetylase through the SMRT-mSin3-HDAC complex (37)(38)(39)(40). Furthermore, the GAGA factor, which appears to be required for RNA polymerase pausing at heat shock promoters (41; for review see 18), is involved in chromatin remodeling (42)(43)(44)(45). The identification of FBI-1 as a POZ domain protein raises the possibility that this factor is involved in establishing a chromatin configuration on the HIV-1 promoter compatible with the synthesis of short transcripts.…”

Section: Introductionmentioning

confidence: 99%

FBI-1, a factor that binds to the HIV-1 inducer of short transcripts (IST), is a POZ domain protein

Morrison

Pendergrast

Stavropoulos

et al. 1999

Nucleic Acids Research

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The HIV-1 promoter directs the synthesis of two classes of transcripts, short, non-polyadenylated transcripts and full-length, polyadenylated transcripts. The synthesis of short transcripts is activated by a bipartite DNA element, the inducer of short transcripts or IST, located downstream of the HIV-1 transcriptional start site, while the synthesis of full-length transcripts is activated by the viral activator Tat. Tat binds to the RNA element TAR, which is encoded largely between the two IST half-elements. Upon activation by Tat, the synthesis of short RNAs is repressed. We have previously purified a factor called FBI-1 (for factor that binds to IST) whose binding to wild-type and mutated ISTs correlated well with the abilities of these ISTs to direct the synthesis of short transcripts. Here, we report the cloning of cDNAs encoding FBI-1. FBI-1 contains a POZ domain at its N-terminus and four Krüppel-type zinc fingers at its C-terminus. The C-terminus is sufficient for specific binding, and FBI-1 can form homomers through its POZ domain and, in vivo, through its zinc finger domain as well. In addition, FBI-1 associates with Tat, suggesting that repression of the short transcripts by Tat may be mediated through interactions between the two factors.

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“…GAGA binding sites have been identified by DNase I footprinting in the proximal promoter regions of 10 Drosophila genes (6,20,28,45,48,51,52). Inspection of these promoter regions reveals that (i) GAGA binding sites cluster in proximal promoter regions of these genes, and the number of distinct binding sites in each ranges between two and seven (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…GAGA sequences have been noted previously in the proximal promoter regions of several Drosophila genes, including Ultrabithorax (Ubx) (6), hsp7O (33), hsp26 (35), E74 (51), Kriippel (28), eve (45), ftz (52), and genes encoding alcohol dehydrogenase (Adh) (4), the laminin B2 chain (11), and histones H3 and H4 (20). Two related models for GAGA protein action have been proposed.…”

mentioning

confidence: 97%

Isolation of cDNAs Encoding the Drosophila GAGA Transcription Factor

Soeller

Kornberg

1993

Molecular and Cellular Biology

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To investigate the mechanisms involved in expression of the Drosophila melanogaster engrailed gene, we purified GAGA protein, one of several putative transcriptional activator proteins that binds to the proximal region of the engrailed promoter. Antibodies raised against GAGA protein were used to demonstrate that the protein is present in all nuclei of young embryos. We isolated cDNA clones encoding GAGA protein in which a putative 519-codon open reading frame contains general sequence motifs characteristic of other transcription factors. These include stretches of polyglutamine, a 60-amino-acid region with 18 (30%) lysine or arginine residues, and a single putative zinc finger motif. In addition, a 120-residue N-terminal region shares significant sequence homology with several other known Drosophila transcription factors, including those encoded by Broad Complex and tramtrack. Up to 35-fold GAGA protein-dependent stimulation of transcription in Schneider line 2 tissue culture cells was observed after transfection of GAGA protein-encoding sequences. The GAGA gene is present in one copy in the Drosophila genome, at cytological location 70EF, and it encodes RNAs which vary in size between 2.4 and 4.4 kb.

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Sequence-specific transcriptional antirepression of the Drosophila Krüppel gene by the GAGA factor.

Cited by 106 publications

References 38 publications

MeCP2 Is a Transcriptional Repressor with Abundant Binding Sites in Genomic Chromatin

MeCP2 Is a Transcriptional Repressor with Abundant Binding Sites in Genomic Chromatin

FBI-1, a factor that binds to the HIV-1 inducer of short transcripts (IST), is a POZ domain protein

Isolation of cDNAs Encoding the Drosophila GAGA Transcription Factor

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