"Here we report the cloning and characterization of a novel protein RIF1 (receptor interacting factor) that interacts with RARalpha in vivo and in vitro."

"GST-pull down assays show that RIF1 also interacts with a number of other NRs. The interaction domain of RIF1 for RARalpha is located at the C-terminal region of RIF1, between amino acids 512 and 674."

"RIF1 is localized exclusively in the cell nucleus and specifically to the nuclear matrix. Mutation of the nuclear localization signal abolishes this nuclear localization and causes RIF1 to appear in the cytoplasm."

"RIF1 contains a strong transcriptional repression domain that robustly inhibits ligand-dependent transcriptional activation by RARalpha. This domain is located to the distal C-terminal 100 amino acids, distinct from the RARalpha-interaction and nuclear matrix-targeting domains. The transcriptional repression activity of RIF1 is mediated at least in part through direct recruitment of histone deacetylases."

"Here we show that Xi compaction requires HBiX1, a heterochromatin protein 1 (HP1)-binding protein, and structural maintenance of chromosomes hinge domain-containing protein 1 (SMCHD1), both of which are enriched throughout the Xi chromosome."

"HBiX1 localization to H3K9me3 and XIST-associated H3K27me3 (XIST-H3K27me3) domains was mediated through interactions with HP1 and SMCHD1, respectively."

"Furthermore, HBiX1 was required for SMCHD1 localization to H3K9me3 domains. Depletion of HBiX1 or SMCHD1, but not Polycomb repressive complex 2 (PRC2), resulted in Xi decompaction, similarly to XIST depletion."

"Thus, the molecular network involving HBiX1 and SMCHD1 links the H3K9me3 and XIST-H3K27me3 domains to organize the compact Xi structure."

"telomere-associated polypeptides including all THO subunits, SMCHD1 and LRIF1."

"with long telomeres."

"Here, we identified a PXVXL-containing protein, ligand-dependent nuclear receptor-interacting factor 1 (LRIF1), which recruits HP1α to the centromere of mitotic chromosomes and its interaction with HP1α is essential for accurate chromosome segregation during mitosis."

"LRIF1 interacts directly with HP1α chromoshadow domain via an evolutionarily conserved PXVXL motif within its C-terminus."

"Importantly, the LRIF1-HP1α interaction is critical for Aurora B activity in the inner centromere. Mutation of PXVXL motif of LRIF1 leads to defects in HP1α centromere targeting and aberrant chromosome segregation."

"We further show that the principal mechanism for chromatin loading of SMCHD1 involves an LRIF1-mediated interaction with HP1γ at trimethylated histone H3 lysine 9 (H3K9me3)-modified chromatin sites on the chromosome arms."

"A parallel pathway accounts for chromatin loading at a minority of sites, notably the inactive X chromosome."

"Proteomic screening revealed that SMCHD1 interacts with LRIF1, the mouse homolog of HBiX1, and with HP1 protein paralogs."

"This mutation resulted in the absence of the long isoform of LRIF1 protein, D4Z4 chromatin relaxation, and DUX4 and DUX4 target gene expression in myonuclei, all molecular and epigenetic hallmarks of FSHD."

"In concordance, LRIF1 was shown to bind to the D4Z4 repeat, and knockdown of the LRIF1 long isoform in muscle cells results in DUX4 and DUX4 target gene expression."

"This study further reinforces the unifying genetic mechanism, which postulates that FSHD is caused by D4Z4 chromatin relaxation, resulting in inappropriate DUX4 expression in skeletal muscle."

"We show that somatic loss-of-function of either SMCHD1 or LRIF1 does not result in D4Z4 chromatin changes and that SMCHD1 and LRIF1 form an auxiliary layer of D4Z4 repressive mechanisms."

"We uncover that SMCHD1, together with the long isoform of LRIF1, binds to the LRIF1 promoter and silences LRIF1 expression."

"The interdependency of SMCHD1 and LRIF1 binding differs between D4Z4 and the LRIF1 promoter, and both loci show different transcriptional responses to either early developmentally or somatically perturbed chromatin function of SMCHD1 and LRIF1."