The human genome is a mosaic of long, compositionally homogeneous DNA segme
nts, 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 fa
milies (H1, H2 and H3), representing 24%, 7.5% and 4-5% of the genome, resp
ectively. Gene concentration increases with increasing GC levels, reaching
a level 20-fold higher in H3 compared with L isochores. In-situ hybridizati
on of DNA from different isochore families provides, therefore, information
on the chromosomal distribution of genes. Using this approach, three subse
ts of reverse or Giemsa-negative bands, H3(+), H3* and H3(-), containing la
rge, moderate, and no detectable amounts, respectively, of the gene-richest
H3 isochores were identified at a resolution of 400 bands. H3(+) bands lar
gely coincide with the most heat-denaturation-resistant bands, the chromomy
cin-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 huma
n genome regions, having an average size of 4 Mb, that are endowed with the
highest gene density.