Biochemical and molecular predictors for prognosis in nonketotic hyperglycinemia.

Objective: Nonketotic hyperglycinemia is a neurometabolic disorder characterized by intellectual disability, seizures, and spasticity. Patients with attenuated nonketotic hyperglycinemia make variable developmental progress. Predictive factors have not been systematically assessed.

Proteomic characterization of the nucleolar linker histone H1 interaction network.

To investigate the relationship between linker histone H1 and protein-protein interactions in the nucleolus, we used biochemical and proteomics approaches to characterize nucleoli purified from cultured human and mouse cells. Mass spectrometry identified 175 proteins in human T cell nucleolar extracts that bound to Sepharose-immobilized H1 in vitro. Gene ontology analysis found significant enrichment for H1 binding proteins with functions related to nucleolar chromatin structure and RNA polymerase I transcription regulation, rRNA processing, and mRNA splicing.

Activator-dependent acetylation of chromatin model systems.

Regulatory mechanisms underlying eukaryotic gene expression, and many other DNA metabolic pathways, are tightly coupled to dynamic changes in chromatin architecture in the nucleus. Activation of gene expression generally requires the recruitment of histone acetyltransferases (HATs) to gene promoters by sequence-specific DNA-binding transcriptional activators. HATs often target specific lysines in the core histone amino-terminal "tail" domains (NTDs), which have the potential ability to alter higher order chromatin structure.

Nucleosome distribution and linker DNA: connecting nuclear function to dynamic chromatin structure.

Genetic information in eukaryotes is managed by strategic hierarchical organization of chromatin structure. Primary chromatin structure describes an unfolded nucleosomal array, often referred to as "beads on a string". Chromatin is compacted by the nonlinear rearrangement of nucleosomes to form stable secondary chromatin structures.

Activator-dependent p300 acetylation of chromatin in vitro: enhancement of transcription by disruption of repressive nucleosome-nucleosome interactions.

Condensation of chromatin into higher order structures is mediated by intra- and interfiber nucleosome-nucleosome interactions. Our goals in this study were to determine the impact specific activator-dependent histone acetylation had on chromatin condensation and to ascertain whether acetylation-induced changes in chromatin condensation were related to changes in RNA polymerase II (RNAPII) activity. To accomplish this, an in vitro model system was constructed in which the purified transcriptional activators, Tax and phosphorylated CREB (cAMP-response element-binding protein), recruited the p300 histone acetyltransferase to nucleosomal templates containing the human T-cell leukemia virus type-1 promoter sequences.