Disease relevance of D1

• SAGE analysis of neuroblastoma reveals a high expression of the human homologue of the Drosophila Delta gene [1].

High impact information on D1

• D1 may be involved in formation of the highly compact structure of satellite heterochromatin [2].
• Selective arrangement of ubiquitinated and D1 protein-containing nucleosomes within the Drosophila genome [2].
• The DNA sequence of a cDNA clone representing the predominant transcripts of the locus indicates that D1 encodes a transmembrane protein homologous to blood coagulation factors and epidermal growth factor [3].
• Delta (D1) is required for normal segregation of the embryonic ectoderm into neural and epidermal cell lineages in Drosophila melanogaster [3].
• The relationship between coding sequences and transcript-specific exons within the locus suggests that D1 encodes multiple translational products [3].

Biological context of D1

• Clones encoding this polypeptide have been isolated from a lambda gt11 cDNA library by immunological screening with a D1 antiserum [4].
• Drosophila melanogaster D1 is a satellite DNA-associated protein which preferentially binds DNA sequences containing runs of AT base pairs [4].
• In addition, the multicopy BE28 element maps to pericentric regions of the D. melanogaster 2L, 2R and X chromosome arms to which D1 has been shown to localize [5].
• The titers of the HMG proteins HMGD, HMGZ, and D1 are highest in ovaries and at the beginning of embryonic development [6].
• Using site specific antibodies against helices I and III of HMGD and HMGZ and against the AT-hook motif of D1, protein-specific staining patterns have been observed during embryonic development [6].

Anatomical context of D1

• Loss-of-function mutations in D1 and other zygotic neurogenic loci lead to expansion of the neuroblast population at the expense of the dermoblast population within the ectoderm [3].
• D1 mRNA levels subsequently decrease throughout later development, followed by the accumulation of the D1 protein in adult gonads, where two distributions of D1 can be correlated to different states of gene activity [7].
• The distribution of D1 in salivary gland polytene chromosomes was investigated by immunofluorescence [8].
• The binding of D1 to N in the extracellular space somehow interferes with the N-mediated cytoplasmic retention of Su(H), resulting in the nuclear translocation and "activation" of Su(H) [9].
• Genetic studies in the mouse point to a major role for the Notch-Delta signalling pathway in somite formation [10].

Associations of D1 with chemical compounds

• D1 is soluble in 5% perchloric acid and extractable from nuclei by solutions of moderate ionic strength (0.35 M NaCl) [8].
• It is proposed that C1 proteins, as well as Drosophila D1 [Rodríguez Alfageme et al. (1980) Chromosoma, 78, 1-31] are representative of a class of insect-specific HMG proteins [11].

Other interactions of D1

• We propose that the BE28 repeat clusters could fulfill a similar function, acting as a local boundary between hetero- and euchromatin in a process involving interactions between the BEAF and D1 proteins [5].
• The phenotypes associated with the expression of secreted Delta (DlS) or secreted Serrate (SerS) forms mimic loss-of-function mutations in the Notch pathway [12].
• Both genetic interactions between DlS or SerS transgenics and duplications or loss-of-function mutations of Delta or Serrate indicate that DlS and SerS behave as dominant negative mutations [12].
• While the inactivation is likely to be mediated by a dominant negative effect over Notch, the activation is similar to that elicited by Delta and requires the product of the Suppressor of Hairless gene [13].

Analytical, diagnostic and therapeutic context of D1

• In order to interpret these results and to relate them to the in vivo distribution of D1, we have investigated the pattern of immunofluorescence staining as a function of the methods of chromosome preparation and salivary gland fixation [8].

References