Variegation in Drosophila is a manifest illustration of the important role played by chromatin structure in gene expression. We have isolated mutants of modulo (mod) and shown that this gene is a dominant suppressor of variegation. Null mutants are recessive lethal with a melanotic tumour phenotype. The mod protein directly binds DNA, which indicates that it may serve to anchor multimeric complexes promoting chromatin compaction and silencing. Using a specific monoclonal antibody we examined by immunocytochemistry the accumulation pattern of mod protein during embryogenesis. The protein is first detected before the blastoderm cellularization in all somatic nuclei, precisely when pericentromeric heterochromatin becomes visible. After the first cell division, mod protein is expressed in lineages of specific embryonic primordia. Based on its dominant phenotype, expression pattern and DNA‐binding activity of its product, we propose that mod regulates chromatin structure and activity in specific cell lineages.

The regulatory functions of transcription factors encoded by the Ultrabithorax (Ubx) gene initiate genetic programmes essential for segmental identity and morphogenesis in Drosophila. Based on the formation of DNA‐protein adducts in intact nuclei and immunoselection procedure, we cloned genomic targets for Ubx proteins. One clone was studied in detail. It encompasses parts of the last intron and exon of the scabrous (sca) gene, which encodes a secreted protein involved in cellular communication during neurogenesis. Five motifs, presenting the ATTA core, which is shared by most homeodomain binding sites, were found in the nucleotide sequence of this clone. We detail here the dynamic pattern of sca transcript accumulation during embryogenesis and show that mutation of Ubx results in the ectopic transcription of sca in the first abdominal segment. We propose that a direct interaction of Ubx with cis‐acting elements in sca negatively regulates the gene. Transcript localization in several combinations of deficiencies in the Bithorax complex (BX‐C) indicates that sca is downregulated by abdominal A (abdA) and Abdominal B (AbdB), and suggests that it is a common target of the three genes of BX‐C.

We have cloned, following an immunological screen of an expression library, five cDNA clones encoding the modulo antigen, a DNA-binding protein differentially expressed during Drosophila development. In addition a series of overlapping cDNA and genomic clones were also isolated. This protein is the product of a 2.2 kb mRNA that is encoded by a single genetic locus (100F). Analysis of the complete 544 amino-acid sequence, deduced from nucleotide sequence of cDNAs, shows that the polypeptide exhibits a primary structure with distinct charged regions, a modular structure found in several eukaryotic nuclear proteins, either transcription regulators or structural factors. The amino and carboxyl termini are rich in basic residues. The first third of the sequence contains a long domain comprised almost entirely of glutamic and aspartic acid residues. A typical cAMP dependent phosphorylation site and five potential glycosylation sites have been detected in the amino-acid sequence. Computer searches fail to reveal any significant homology with known proteins. Developmental pattern of transcription of the modulo gene indicates that messengers are maternally provided to the embryos and that zygotic transcription is required during subsequent development.