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Co-localization of Polycomb protein and GAGA factor on regulatory elements responsible for the maintenance of homeotic gene expression.

ABSTRACT: The Polycomb group and trithorax group genes of Drosophila are required for maintaining the differential expression state of developmental regulators, such as the homeotic genes, in a stable and heritable manner throughout development. The Polycomb group genes have been suggested to act by regulating higher order chromatin and packaging repressed chromosomal domains in a heterochromatin-like structure. We have mapped, at high resolution, the distribution of Polycomb protein on the bithorax complex of Drosophila tissue culture cells, using an improved formaldehyde cross-linking and immunoprecipitation technique. Polycomb protein is not distributed homogeneously on the regulatory regions of the repressed Ultrabithorax and abdominal-A genes, but is highly enriched at discrete sequence elements, many of which coincide with previously mapped Polycomb group response elements (PREs). Our results further suggest that Polycomb protein spreads locally over a few kilobases of DNA surrounding PREs, perhaps to stabilize silencing complexes. GAGA factor/Trithorax-like, a member of the trithorax group, is also bound at those PREs which contain GAGA consensus-binding sites. Two modes of binding can be distinguished: a high level binding to elements in the regulatory domain of the expressed Abdominal-B gene, and a low level of binding to Polycomb-bound PREs in the inactive domains of the bithorax complex. We propose that GAGA factor binds constitutively to regulatory elements in the bithorax complex, which function both as PREs and as trithorax group response elements.

SUBMITTER: Strutt H

PROVIDER: S-EPMC1169986 | biostudies-other | 1997 Jun

REPOSITORIES: biostudies-other

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Co-localization of Polycomb protein and GAGA factor on regulatory elements responsible for the maintenance of homeotic gene expression.

Strutt H H Cavalli G G Paro R R

The EMBO journal 19970601 12

The Polycomb group and trithorax group genes of Drosophila are required for maintaining the differential expression state of developmental regulators, such as the homeotic genes, in a stable and heritable manner throughout development. The Polycomb group genes have been suggested to act by regulating higher order chromatin and packaging repressed chromosomal domains in a heterochromatin-like structure. We have mapped, at high resolution, the distribution of Polycomb protein on the bithorax compl ...[more]

PMID: 9218803

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Project description:BACKGROUND: Hox genes impart segment identity to body structures along the anterior-posterior axis and are crucial for the proper development of all organisms. Multiple regulatory elements, best defined in Drosophila melanogaster, ensure that Hox expression patterns follow the spatial and temporal colinearity reflected in their tight genomic organization. However, the precise mechanisms that regulate colinear patterns of Hox gene expression remain unclear, especially in higher vertebrates where it is not fully determined how the distinct activation domains of the tightly clustered Hox genes are defined independently of each other. Here, we report the identification of a large number of novel cis-elements at mammalian Hox clusters that can help in regulating their precise expression pattern. RESULTS: We have identified DNA elements at all four murine Hox clusters that show poor association with histone H3 in chromatin immunoprecipitation (ChIP)-chip tiling arrays. The majority of these elements lie in the intergenic regions segregating adjacent Hox genes; we demonstrate that they possess efficient enhancer-blocking activity in mammalian cells. Further, we find that these histone-free intergenic regions bear GA repeat motifs and associate with the vertebrate homolog of the GAGA binding boundary factor. This suggests that they can act as GAGA factor-dependent chromatin boundaries that create independent domains, insulating each Hox gene from the influence of neighboring regulatory elements. CONCLUSIONS: Our results reveal a large number of potential regulatory elements throughout the murine Hox clusters. We further demarcate the precise location of several novel cis-elements bearing chromatin boundary activity that appear to segregate successive Hox genes. This reflects a pattern reminiscent of the organization of homeotic genes in Drosophila, where such regulatory elements have been characterized. Our findings thus provide new insights into the regulatory processes and evolutionarily conserved epigenetic mechanisms that control homeotic gene expression.

Dataset Information

Co-localization of Polycomb protein and GAGA factor on regulatory elements responsible for the maintenance of homeotic gene expression.

Publications

Co-localization of Polycomb protein and GAGA factor on regulatory elements responsible for the maintenance of homeotic gene expression.

Similar Datasets

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