Maintenance of stable heterochromatin domains by dynamic HP1 binding.
One function of heterochromatin is the epigenetic silencing by sequestration of genes into transcriptionally repressed nuclear neighborhoods. Heterochromatin protein 1 (HP1) is a major component of heterochromatin and thus is a candidate for establishing and maintaining the transcriptionally repressive heterochromatin structure. Here we demonstrate that maintenance of stable heterochromatin domains in living cells involves the transient binding and dynamic exchange of HP1 from chromatin. HP1 exchange kinetics correlate with the condensation level of chromatin and are dependent on the histone methyltransferase Suv39h. The chromodomain and the chromoshadow domain of HP1 are both required for binding to native chromatin in vivo, but they contribute differentially to binding in euchromatin and heterochromatin. These data argue against HP1 repression of transcription by formation of static, higher order oligomeric networks but support a dynamic competition model, and they demonstrate that heterochromatin is accessible to regulatory factors.
Cheutin
Thierry
T
National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
McNairn
Adrian J
AJ
Jenuwein
Thomas
T
Gilbert
David M
DM
Singh
Prim B
PB
Misteli
Tom
T
D000546:Amanitins / Q000494:pharmacology; D000818:Animals; D001665:Binding Sites; D016466:CHO Cells; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D000090266:Chromobox Protein Homolog 5; D002868:Chromosomal Proteins, Non-Histone / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006224:Cricetinae; D019281:Dimerization; D022041:Euchromatin / Q000378:metabolism; D036681:Fluorescence Recovery After Photobleaching; D006367:HeLa Cells; D006570:Heterochromatin / Q000737:chemistry* / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D007700:Kinetics; D008780:Methyltransferases / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014162:Transfection
D000546:Amanitins; D002868:Chromosomal Proteins, Non-Histone; D022041:Euchromatin; D006570:Heterochromatin; D006657:Histones; D006877:Hydroxamic Acids; D011993:Recombinant Fusion Proteins; D000090266:Chromobox Protein Homolog 5; C012589:trichostatin A; D008780:Methyltransferases