PMID- 10330177
OWN - NLM
STAT- MEDLINE
DCOM- 19990617
LR  - 20190508
IS  - 0270-7306 (Print)
IS  - 0270-7306 (Linking)
VI  - 19
IP  - 6
DP  - 1999 Jun
TI  - KAP-1 corepressor protein interacts and colocalizes with heterochromatic and
      euchromatic HP1 proteins: a potential role for Kruppel-associated box-zinc finger
      proteins in heterochromatin-mediated gene silencing.
PG  - 4366-78
AB  - Kruppel-associated box (KRAB) domains are present in approximately one-third of
      all human zinc finger proteins (ZFPs) and are potent transcriptional repression
      modules. We have previously cloned a corepressor for the KRAB domain, KAP-1,
      which is required for KRAB-mediated repression in vivo. To characterize the
      repression mechanism utilized by KAP-1, we have analyzed the ability of KAP-1 to 
      interact with murine (M31 and M32) and human (HP1alpha and HP1gamma) homologues
      of the HP1 protein family, a class of nonhistone heterochromatin-associated
      proteins with a well-established epigenetic gene silencing function in
      Drosophila. In vitro studies confirmed that KAP-1 is capable of directly
      interacting with M31 and hHP1alpha, which are normally found in centromeric
      heterochromatin, as well as M32 and hHP1gamma, both of which are found in
      euchromatin. Mapping of the region in KAP-1 required for HP1 interaction showed
      that amino acid substitutions which abolish HP1 binding in vitro reduce KAP-1
      mediated repression in vivo. We observed colocalization of KAP-1 with M31 and M32
      in interphase nuclei, lending support to the biochemical evidence that M31 and
      M32 directly interact with KAP-1. The colocalization of KAP-1 with M31 is
      sometimes found in subnuclear territories of potential pericentromeric
      heterochromatin, whereas colocalization of KAP-1 and M32 occurs in punctate
      euchromatic domains throughout the nucleus. This work suggests a mechanism for
      the recruitment of HP1-like gene products by the KRAB-ZFP-KAP-1 complex to
      specific loci within the genome through formation of heterochromatin-like
      complexes that silence gene activity. We speculate that gene-specific repression 
      may be a consequence of the formation of such complexes, ultimately leading to
      silenced genes in newly formed heterochromatic chromosomal environments.
FAU - Ryan, R F
AU  - Ryan RF
AD  - The Wistar Institute, Philadelphia, Pennsylvania, USA.
FAU - Schultz, D C
AU  - Schultz DC
FAU - Ayyanathan, K
AU  - Ayyanathan K
FAU - Singh, P B
AU  - Singh PB
FAU - Friedman, J R
AU  - Friedman JR
FAU - Fredericks, W J
AU  - Fredericks WJ
FAU - Rauscher, F J 3rd
AU  - Rauscher FJ 3rd
LA  - eng
GR  - P30 DK050306/DK/NIDDK NIH HHS/United States
GR  - P30 CA010815/CA/NCI NIH HHS/United States
GR  - CA 52009/CA/NCI NIH HHS/United States
GR  - T32 CA009171/CA/NCI NIH HHS/United States
GR  - P01 DK049210/DK/NIDDK NIH HHS/United States
GR  - CA 09171/CA/NCI NIH HHS/United States
GR  - DK 49210/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Mol Cell Biol
JT  - Molecular and cellular biology
JID - 8109087
RN  - 0 (Cbx1 protein, mouse)
RN  - 0 (Chromatin)
RN  - 0 (Chromosomal Proteins, Non-Histone)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Euchromatin)
RN  - 0 (Heterochromatin)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Repressor Proteins)
RN  - 0 (Transcription Factors)
RN  - 107283-02-3 (heterochromatin-specific nonhistone chromosomal protein HP-1)
RN  - EC 1.13.12.- (Luciferases)
RN  - EC 2.3.2.27 (Trim28 protein, mouse)
RN  - EC 2.3.2.27 (Tripartite Motif-Containing Protein 28)
SB  - IM
MH  - 3T3 Cells
MH  - Animals
MH  - Blotting, Western
MH  - COS Cells
MH  - Cell Nucleus/metabolism
MH  - Chromatin/metabolism
MH  - Chromatography, Liquid
MH  - Chromosomal Proteins, Non-Histone/metabolism/*physiology
MH  - DNA-Binding Proteins/*physiology
MH  - Electrophoresis, Polyacrylamide Gel
MH  - Euchromatin
MH  - Fluorescent Antibody Technique, Indirect
MH  - *Heterochromatin
MH  - Luciferases/metabolism
MH  - Mice
MH  - Models, Biological
MH  - Models, Genetic
MH  - Mutagenesis
MH  - *Nuclear Proteins
MH  - Protein Binding
MH  - Protein Conformation
MH  - Recombinant Fusion Proteins
MH  - Repressor Proteins/metabolism/*physiology
MH  - *Transcription Factors
MH  - Transfection
MH  - Tripartite Motif-Containing Protein 28
MH  - Zinc Fingers/*physiology
PMC - PMC104396
EDAT- 1999/05/18 05:26
MHDA- 2001/03/28 10:01
CRDT- 1999/05/18 05:26
PHST- 1999/05/18 05:26 [pubmed]
PHST- 2001/03/28 10:01 [medline]
PHST- 1999/05/18 05:26 [entrez]
AID - 10.1128/mcb.19.6.4366 [doi]
PST - ppublish
SO  - Mol Cell Biol. 1999 Jun;19(6):4366-78. doi: 10.1128/mcb.19.6.4366.