The trithorax gene, a trans-acting regulator of the bithorax complex in Drosophila, encodes a protein with zinc-binding domains.

Mazo, Alexander; Huang, Der-Hwa; Mozer, Brian A.; Dawid, Igor B.

doi:10.1073/pnas.87.6.2112

Cited by 177 publications

(148 citation statements)

References 36 publications

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“…There are currently little experimental data on the functional role of the LAP/PHD domain. Fusion constructs of Drosophila TRX containing the LAP/PHD domain were used to demonstrate that this region could bind zinc more strongly than other cysteine rich regions within this protein (Mazo et al, 1990). The N terminus of the plant protein HAT3.1 contains a LAP/PHD motif and it can bind non-speci®cally in vitro to any fragment of DNA greater than 100 bp (Schindler et al, 1993).…”

Section: Discussionmentioning

confidence: 99%

The cloning, mapping and expression of a novel gene, BRL, related to the AF10 leukaemia gene

McCullagh¹,

Chaplin²,

Meerabux³

et al. 1999

Oncogene

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The MLL gene is reciprocally translocated with one of a number of di erent partner genes in a proportion of human acute leukaemias. The precise mechanism of oncogenic transformation is unclear since most of the partner genes encode unrelated proteins. However, two partner genes, AF10 and AF17 are related through the presence of a cysteine rich region and a leucine zipper. The identi®cation of other proteins with these structures will aid our understanding of their role in normal and leukaemic cells. We report the cloning of a novel human gene (BRL) which encodes a protein containing a cysteine rich region related to that of AF10 and AF17 and is overall most closely related to the previously known protein BR140. BRL maps to chromosome 22q13 and shows high levels of expression in testis and several cell lines. The deduced protein sequence also contains a bromodomain, four potential LXXLL motifs and four predicted nuclear localization signals. A monoclonal antibody raised to a BRL peptide sequence con®rmed its widespread expression as a 120 Kd protein and demonstrated localization to the nucleus within spermatocytes.

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Section: Discussionmentioning

confidence: 99%

The cloning, mapping and expression of a novel gene, BRL, related to the AF10 leukaemia gene

McCullagh¹,

Chaplin²,

Meerabux³

et al. 1999

Oncogene

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“…Candidates for later acting en regulators, both positive and negative, have been identified among the trithorax and Polycomb gene classes. Mutations in these genes have been found to affect maintenance of expression patterns of homeotic selector genes [23][24][25] , and members of the Polycomb class have been shown to affect en expression as well (D. Moazed and P.O'F., unpublished data) [26][27][28] The classically defined stages of reversible and irreversible cell fate commitment lead us to expect changes in the mode of en regulation during development. But the elaborate progression that we have uncovered is difficult to rationalize in all its detail.…”

Section: Progression To Determinationmentioning

confidence: 99%

Multiple modes of engrailed regulation in the progression towards cell fate determination

Heemskerk

DiNardo

Kostriken³

et al. 1991

Nature

249

147

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The engrailed gene product of Drosophila specifies the fate of a subset of cells in each segment. Our studies of engrailed regulation suggest that fate determination is an elaborate, multistep process. At the time in embryogenesis when the engrailed-dependent cell fate is probably determined, four modes of control act in an overlapping progression to govern engrailed expression. After activation by pairrule genes, both an extracellular signal, wingless, and autoregulation are required for engrailed expression. Autoregulation graduates to wingless independence, but is transient, and is superseded by an engrailed-independent mode of maintenance.Two levels of commitment have been defined for the choice of cell fate 1 . Early in development, fate can be instructed by environmental cues. This fate specification is flexible and allows fate to change in response to extracellular signals. But cells can undergo a transition from this type of specification to one which is determined and therefore irreversible. Because a determined cell maintains a particular fate independent of its environment, the transition to a determined state requires that development comes under cell-intrinsic, rather than cell-extrinsic control. The identification of selector genes in Drosophila provides an opportunity to study the basis of both types of cell-fate control. Selector genes encode regulators whose function defines the fate of a cell, and whose continued expression stably maintains cell fate 2,3 . Where the choice of cell fate is initially dependent on the environment, selector gene expression must be sensitive to extracellular signals. By contrast, once cell fate is determined, expression of these genes must be governed exclusively by cell-intrinsic factors.The engrailed (en) gene is a selector gene that distinguishes two populations of cells in each developing embryonic segment, the progenitors of the anterior and posterior compartments 3,4 . This distinction can be seen as a lineage restriction when individual embryonic cells are marked by mitotic recombination 5,6 . These give rise to clonal patches in the adult that never span the boundary between the anterior and posterior compartments, demonstrating that, from the time of marking, the progeny of a given cell only contribute to one compartment. This restriction requires expression of en by posterior cells 3,4,7 . But it seems that the onset of localized en expression in early embryos is not sufficient to irreversibly determine posterior compartment identity because en requires at least one cell-extrinsic input at this time.This input is provided by the wingless (wg) gene, expressed in segmentally repeated stripes of cells that lie next to en-expressing cells 8,9 . The wg protein, which is homologous to the product of the proto-oncogene Wnt-1 ( ref. 10 ), is secreted and appears to be taken up by en-expressing cells 9 . In wg mutant embryos, en expression is initiated in a normal striped pattern but soon stops, indicating that continued en expression in wild-type embryos r...

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“…ALL-1 shares homology with its Drosophila homologue TRITHORAX (TRX) (Mazo et al, 1990) in two major and at least two minor domains. The latter were implicated in the distribution of the ALL-1 protein in nuclear speckles .…”

Section: Introductionmentioning

confidence: 99%

Self-association of the SET domains of human ALL-1 and of Drosophila TRITHORAX and ASH1 proteins

et al. 2000

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The human ALL-1 gene is involved in acute leukemia through gene fusions, partial tandem duplications or a speci®c deletion. Several sequence motifs within the ALL-1 protein, such as the SET domain, PHD ®ngers and the region with homology to DNA methyl transferase are shared with other proteins involved in transcription regulation through chromatin alterations. However, the function of these motifs is still not clear. Studying ALL-1 presents an additional challenge because the gene is the human homologue of Drosophila trithorax. The latter is a member of the trithorax-Polycomb gene family which acts to determine the body pattern of Drosophila by maintaining expression or repression of the Antennapedia-bithorax homeotic gene complex. Here we apply yeast two hybrid methodology, in vivo immunoprecipitation and in vitro`pull down' techniques to show self association of the SET motifs of ALL-1, TRITHORAX and ASH1 proteins (Drosophila ASH1 is encoded by a trithoraxgroup gene). Point mutations in evolutionary conserved residues of TRITHORAX SET, abolish the interaction. SET ± SET interactions might act in integrating the activity of ALL-1 (TRX and ASH1) protein molecules, simultaneously positioned at di erent maintenance elements and directing expression of the same or di erent target genes. Oncogene (2000) 19, 351 ± 357.

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The trithorax gene, a trans-acting regulator of the bithorax complex in Drosophila, encodes a protein with zinc-binding domains.

Abstract: The trithorax (trx) gene functions in segment determination in Drosophika through interaction with genes of

Cited by 177 publications

References 36 publications

The cloning, mapping and expression of a novel gene, BRL, related to the AF10 leukaemia gene

The cloning, mapping and expression of a novel gene, BRL, related to the AF10 leukaemia gene

Multiple modes of engrailed regulation in the progression towards cell fate determination

Self-association of the SET domains of human ALL-1 and of Drosophila TRITHORAX and ASH1 proteins

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