No abstract

The human transcription factor DNA replication-related element-binding factor (hDREF) is essential for the transcription of a number of housekeeping genes. The mechanisms underlying constitutively active transcription by hDREF were unclear. Here, we provide evidence that hDREF possesses small ubiquitin-like modifier (SUMO) ligase activity and can specifically SUMOylate Mi2␣, an ATP-dependent DNA helicase in the nucleosome remodeling and deacetylation complex. Moreover, immunofluorescent staining and biochemical analyses showed that coexpression of hDREF and SUMO-1 resulted in dissociation of Mi2␣ from chromatin, whereas a SUMOylation-defective Mi2␣ mutant remained tightly bound to chromatin. Chromatin immunoprecipitation and quantitative RT-PCR analysis demonstrated that Mi2␣ expression diminished transcription of the ribosomal protein genes, which are positively regulated by hDREF. In contrast, coexpression of hDREF and SUMO-1 suppressed the transcriptional repression by Mi2␣. These data indicate that hDREF might incite transcriptional activation by SUMOylating Mi2␣, resulting in the dissociation of Mi2␣ from the gene loci. We propose a novel mechanism for maintaining constitutively active states of a number of hDREF target genes through SUMOylation.

Key wordsbiliary atresia, urinary sulfated bile acid.A selective screening for an early identification of biliary atresia (BA) and hepatobiliary disease is advocated 1 using tests for urinary bilirubin and serum direct bilirubin in the third week of life. However, venepuncture is not desirable in small infants for a primary screening purpose at a clinic. The urinary excretion of sulfated bile acid (USBA) increases with cholestasis through an activated alternate metabolic pathway of bile acid. 2 A direct enzymatic assay of USBA has been reported as a sensitive and rapid method of detecting cholestatic jaundice, replacing measurements of serum-direct bilirubin for selective screening for BA and neonatal hepatitis syndrome. 3 We have measured USBA in BA before surgery and other infantile cholestatic conditions since 1996. The present report summarizes the feasibility of this urinary test as a screening modality.

Postoperative intussusception in the newborn is an infrequent condition. A 17-day-old female with duodenal stenosis and malrotation underwent excision of the membrane in the duodenum and incidental appendicectomy. Postoperatively, a ceco-colic type of intussusception occurred, necessitating a right hemicolectomy. We speculate that the causative factors are twofolds: the embedded appendiceal stump, a polyp-like protrusion that became a lead point, and the non-fixation of the ileocecal mesentery, which facilitated a ceco-colic type of invagination.

Dephosphorylation of lamin A, which triggers nuclear lamina reconstitution, is crucial for the completion of mitosis. However, the specific phosphatase and regulatory mechanism that allow timely lamin A dephosphorylation remain unclear. Here, we report that RepoMan, a regulatory subunit of protein phosphatase 1γ (PP1γ) is transiently modified with SUMO-2 at K762 during late telophase. SUMOylation of RepoMan markedly enhanced its binding affinity with lamin A. Moreover, the SUMOylated RepoMan/PP1γ contributes to lamin A recruitment to telophase chromosomes and dephosphorylation of the mitotic lamin A phosphorylation. Expression of a SUMO-2 mutant defective in interaction with SUMO interacting motif (SIM) resulted in failure of the lamin A and RepoMan association, along with abrogation of lamin A dephosphorylation and subsequent nuclear lamina formation. These findings strongly suggested that RepoMan/PP1γ recruits lamin A through SUMO-SIM interaction. Thus, transient SUMOylation of RepoMan plays an important role in the spatio-temporal regulation of lamin A dephosphorylation and the subsequent nuclear lamina formation at the end of mitosis.