Genomic sequence and transcriptional profile of the boundary between pericentromeric satellites and genes on human chromosome arm 10q

The organization of centromeric heterochromatin has been established in a n umber of eucaryotes but remains poorly defined in human. Here we present 10 25 kb of contiguous human genomic sequence which links pericentromeric sate llites to the RET proto-oncogene in 10q11.2 and is presumed to span the tra nsition from centric heterochromatin to euchromatin on this chromosome arm. Two distinct domains can be defined within the sequence. The proximal simi lar to 240 kb consists of arrays of satellites and other tandem repeats sep arated by tracts of complex sequence which have evolved by pericentromeric- directed duplication, Analysis of 32 human paralogues of these sequences in dicates that most terminate at or within repeat arrays, implicating these r epeats in the interchromosomal duplication process. Corroborative PCR-based analyses establish a genome-wide correlation between the distribution of t hese paralogues and the distribution of satellite families present in 10q11 , In contrast, the distal similar to 780 kb contains few tandem repeats and is largely chromosome specific. However, a minimum of three independent in trachromosomal duplication events have resulted in >370 kb of this sequence sharing >90% identity with sequences on 10p, Using computer-based analyses and RT-PCR we confirm the presence of three genes within the sequence, ZNF 11/33B, KIAA0187 and RET, in addition to five transcripts of unknown struct ure, All of these transcribed sequences map distal to the satellite arrays, The boundary between satellite-rich interchromosomally duplicated DNA and chromosome-specific DNA therefore appears to define a transition from peric entromeric heterochromatin to euchromatin on the long arm of this chromosom e.