Association of transcriptionally silent genes with Ikaros complexes at centromeric heterochromatin.
Ikaros proteins are required for normal T, B, and NK cell development and are postulated to activate lymphocyte-specific gene expression. Here we examined Ikaros distribution in the nucleus of B lymphocytes using confocal microscopy and a novel immunofluorescence in situ hybridization (immuno-FISH) approach. Unexpectedly, Ikaros localized to discrete heterochromatin-containing foci in interphase nuclei, which comprise clusters of centromeric DNA as defined by gamma-satellite sequences and the abundance of heterochromatin protein-1 (HP-1). Using locus-specific probes for CD2, CD4, CD8alpha, CD19, CD45, and lambda5 genes, we show that transcriptionally inactive but not transcriptionally active genes associate with Ikaros-heterochromatin foci. These findings support a model of organization of the nucleus in which repressed genes are selectively recruited into centromeric domains.
Brown
K E
KE
Lymphocyte Development Group, MRC Clinical Sciences Centre, Imperial College School of Medicine, Hammersmith Hospital, London, United Kingdom.
Guest
S S
SS
Smale
S T
ST
Hahm
K
K
Merkenschlager
M
M
Fisher
A G
AG
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D000944:Antigens, Differentiation, B-Lymphocyte / Q000096:biosynthesis / Q000235:genetics; D001402:B-Lymphocytes / Q000502:physiology; D002460:Cell Line; D002467:Cell Nucleus / Q000502:physiology / Q000648:ultrastructure; D002503:Centromere / Q000502:physiology* / Q000648:ultrastructure; D004268:DNA-Binding Proteins; D005786:Gene Expression Regulation; D006570:Heterochromatin / Q000502:physiology* / Q000648:ultrastructure; D051740:Ikaros Transcription Factor; D008223:Lymphoma; D051379:Mice; D008822:Mice, Transgenic; D008957:Models, Genetic; D016133:Polymerase Chain Reaction; D018123:Receptors, Interleukin / Q000096:biosynthesis; D020395:Receptors, Interleukin-7; D014157:Transcription Factors / Q000032:analysis / Q000378:metabolism*; D014158:Transcription, Genetic; D016335:Zinc Fingers
D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D004268:DNA-Binding Proteins; D006570:Heterochromatin; D018123:Receptors, Interleukin; D020395:Receptors, Interleukin-7; D014157:Transcription Factors; C497238:Zfpn1a1 protein, mouse; D051740:Ikaros Transcription Factor