RT Journal
A1 Vogel, Maartje J.
A1 Guelen, Lars
A1 de Wit, Elzo
A1 Hupkes, Daniel Peric
A1 Lodén, Martin
A1 Talhout, Wendy
A1 Feenstra, Marike
A1 Abbas, Ben
A1 Classen, Anne-Kathrin
A1 van Steensel, Bas
T1 Human heterochromatin proteins form large domains containing KRAB-ZNF genes
JF Genome Research 
JO Genome Research 
YR 2006 
FD December 01 
VO 16 
IS 12 
SP 1493 
OP 1504 
DO 10.1101/gr.5391806 
UL http://genome.cshlp.org/content/16/12/1493.abstract 
AB Heterochromatin is important for gene regulation and chromosome structure, but the genes that are occupied by heterochromatin proteins in the mammalian genome are largely unknown. We have adapted the DamID method to systematically identify target genes of the heterochromatin proteins HP1 and SUV39H1 in human and mouse cells. Unexpectedly, we found that CBX1 (formerly HP1β) and SUV39H1 bind to genes encoding KRAB domain containing zinc finger (KRAB-ZNF) transcriptional repressors. These genes constitute one of the largest gene families and are organized in clusters in the human genome. Preference of CBX1 for this gene family was observed in both human and mouse cells. High-resolution mapping on human chromosome 19 revealed that CBX1 coats large domains 0.1–4 Mb in size, which coincide with the position of KRAB-ZNF gene clusters. These domains show an intricate CBX1 binding pattern: While CBX1 is globally elevated throughout the domains, it is absent from the promoters and binds more strongly to the 3′ ends of KRAB-ZNF genes. KRAB-ZNF domains contain large numbers of LINE elements, which may contribute to CBX1 recruitment. These results uncover a surprising link between heterochromatin and a large family of regulatory genes in mammals. We suggest a role for heterochromatin in the evolution of the KRAB-ZNF gene family.