Published in: Human Molecular Genetics, Vol. 9, No. 13, pp. 2029-2042 (2000):

"Genomic Sequence and Transcriptional Profile of the Boundary Between Pericentromeric Satellites and Genes on Human Chromosome Arm 10q".

J. Guy¹, C. Spalluto^1,2, A. McMurray³, T. Hearn¹, M. Crosier¹, L. Viggiano², V. Miolla², N. Archidiacono², M. Rocchi², C. Scott³, P.A. Lee⁴, J. Sulston³, J. Rogers³, D. Bentley³ and M.S. Jackson^1,*

¹Human Genetics Unit, School of Biochemistry and Genetics, University of Newcastle upon Tyne, Newcastle upon Tyne NE1 7RU, UK,
²DAPEG, Sezione di Genetica, Università di Bari, Via Amendola 165/A, 70126 Bari, Italy,
³Sanger Sequencing Centre, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK and ⁴Department of Computer Science, University of Newcastle upon Tyne, Newcastle upon Tyne NE1 7RU, UK

Abstract:
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The organization of centromeric heterochromatin has been established in a number of eucaryotes but remains poorly defined in human. Here we present 1025 kb of contiguous human genomic sequence which links pericentromeric satellites to the RET proto-oncogene in 10q11.2 and is presumed to span the transition from centric heterochromatin to euchromatin on this chromosome arm. Two distinct domains can be defined within the sequence. The proximal ~240 kb consists of arrays of satellites and other tandem repeats separated by tracts of complex sequence which have evolved by pericentromeric-directed duplication. Analysis of 32 human paralogues of these sequences indicates that most terminate at or within repeat arrays, implicating these repeats in the interchromosomal duplication process. Corroborative PCR-based analyses establish a genome-wide correlation between the distribution of these paralogues and the distribution of satellite families present in 10q11. In contrast, the distal ~780 kb contains few tandem repeats and is largely chromosome specific. However, a minimum of three independent intrachromosomal 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, ZNF11/33B, KIAA0187 and RET, in addition to five transcripts of unknown structure. 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 pericentromeric heterochromatin to euchromatin on the long arm of this chromosome.

* To whom correspondence should be addressed. Tel: +44 191 222 8005; Fax: +44 191 222 6662;
Email: mjackson@hgmp.mrc.ac.uk

1. "Mated Models of Gene Regulation in Eukaryotes".

2. "Oncogenes as Molecular Targets within Active Chromatin".