Review
Copyright ©2014 Baishideng Publishing Group Inc.
World J Biol Chem. Aug 26, 2014; 5(3): 308-320
Published online Aug 26, 2014. doi: 10.4331/wjbc.v5.i3.308
Table 1 Chromatin-associated factors/chromatin-remodeling enzymes interacting with KAP1
Chromatin-associated factors/chromatin-remodeling enzymesConsequences of binding with KAP1Ref.
HP1HP1-KAP1 interaction leads to transcriptional repression and has an essential role in development and cell differentiation. Phosphorylation at Ser-473 or Tyr-449, 458, 517 of KAP1 inhibits its interaction with HP1.[5,6,33,43,46,53,94-97,105]
SETDB1KAP1 binds to SETDB1 through SUMO:SIM interaction to methylate H3K9 at gene regulatory regions to achieve gene silencing.[9,15,16,109]
N-CoRN-CoR represses basal transcription by the recruitment of HDACs to deacetylate histones. KAP1 is involved in N-CoR-1 complex to mediate transcriptional repression.[7]
CHD3 (Mi-2α)/NuRDNuRD complex mediates chromatin remodelling and histone deacetylation via CHD3 (Mi-2α) and HDACs, respectively. KAP1 interacts with NuRD complex via PHD and bromodomain to alter the chromatin structure.[8,21,37]
HDAC1KAP1-HDAC1 complex interaction not only regulates histone modification but also non-histone protein deacetylation to exert a variety of different functions (also shown in Table 2).[113]
SMARCAD1SMARCAD1 mediates histone deacetylation and associates with KAP1-HDAC1 complex to regulate chromatin marks.[58]
DNMTKAP1 associates with DNMT to maintain DNA methylation at imprinting control region (also shown in Table 2).[59,61]
Table 2 Transcription factors involved in KAP1-regulated gene expression
Transcription factor KAP1 functionRef.
MycKAP1 is involved in MM-1 and HDAC1 complex to suppress c-Myc transcription activity[10,11]
ZNF160KAP1 interacts with ZNF160 and recruits HDAC to downregulate TLR4 in intestinal epithelial cells[79]
Oct3/4KAP1 is potentially involved in regulating pluripotency of embryonic stem cells[78]
E2F1KAP1 suppresses E2F1 transcriptional activity and inhibits E2F1 acetylation in an HDAC1 dependent manner[13]
p53KAP1 is associated with MDM2-p53-HDAC1 complex and inhibits p53 acetylation and promotes p53 degradation[75]
p53MAGE proteins stabilize KAP1-p53 complex to decrease acetylation and promote degradation of p53[80]
p53KAP1 ubiquitinates p53 for proteasome degradation[23]
IRF7KAP1 sumolyates IRF7 and suppresses IRF7 transcriptional activity in IFN production[24]
ZBRK1KAP1 interacts with ZBRK1 to repress Gadd45α and p21 gene expression[16,17,69]
HIF-1αVHLaK potentially recruits KAP1 to HIF-1α complex to suppress HIF-1α downstream gene expression[72]
Nrf2KAP1 interacts with Nrf2 and facilitates Nrf2 transactivation activity[76]
STAT3KAP1 interacts with STAT3 to suppress STAT3 transcriptional activity[82]
STAT1KAP1 interacts with STAT1 to suppress STAT1 transcriptional activity[50]
ZNF689ZNF689 potentially recruits KAP1 to suppress autophagy-gene-targeting miRNAs[71]
FOXP3KAP1 is recruited by FIK in FOXP3-FIK-KAP1 complex to suppress FOXP3-target genes[74]
NFκBKAP1 is associated with NFκB and negatively regulates it acetylation and transcriptional activity[51]
SRYKAP1 is recruited by KRAB-O to SRY binding sites for gene regulation[68,73]
ZFP57ZFP57 and KAP1 are associated with NP95-DNMT complex for maintaining DNA methylation at imprinting control region[59,61,62]
Table 3 Mouse models illustrating the physiological functions of Kap1
Animal modelPhenotypeRef.
Kap1 knockout miceEmbryonic lethal prior to gastulation[19]
Hemato-specific Kap1 knockout miceImpaired erythropoiesis[71,100]
T-cell-specific Kap1 knockout miceDefective T-cell differentiation[48,98]
B-cell-specific Kap1 knockout miceDefective B-cell differentiation[99]
Tamoxifen-inducible-germ cell-lineage-specific Kap1 depletion miceImpaired spermatogenesis[101]
Liver-specific Kap1 knockout miceMale-predominant steatosis and hepatic adenoma[120]
Kap1 knockout in mice forebrainAnxiety-like-behavior and cognitive impairments[103]