Identification of the gene-richest bands in human prometaphase chromosomes

The human genome is a mosaic of long, compositionally homogeneous DNA segments, the isochores, that can be partitioned into five families, two GC-poor families (L1 and L2), representing 63% of the genome, and three GC-rich families (H1, H2 and H3), representing 24%, 7.5% and 4-5% of the genome, respectively. Gene concentration increases with increasing GC levels, reaching a level 20-fold higher in H3 compared with L isochores. In-situ hybridization of DNA from different isochore families provides, therefore, information on the chromosomal distribution of genes. Using this approach, three subsets of reverse or Giemsa-negative bands, H3(+), H3* and H3(-), containing large, moderate, and no detectable amounts, respectively, of the gene-richest H3 isochores were identified at a resolution of 400 bands. H3(+) bands largely coincide with the most heat-denaturation-resistant bands, the chromomycin-A3-positive, DAPI-negative bands, the bands with the highest CpG island concentrations, and the earliest replicating bands. Here, we have defined the H3(+) bands at a 850-band resolution, and have thus identified the human genome regions, having an average size of 4 Mb, that are endowed with the highest gene density.