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Research has been conducted on the E1A binding protein complex. The identification of this complex which is essential for the E1A-mediated transformation has been carried out and the results are reported.

The establishment of cell lines that express epitope-tagged Brg1 and hBrm and characterization of the complexes associated with the two ATPases are described. Brg1 has been found to fractionate into two complexes different in subunit composition and activity, but hBrm is seen in cone complex with lower activity than the Brg1 complexes. Unexpected functional characteristics show the hSWI/SNF complexes under consideration rave diverse regulatory functions. Evidence that the Brg1 and hBrm complexes have in them subunits of the human Sin3 complex has been seen.

Research was conducted to examine the mechanism of hSWI/SNF remodeling of a nucleosome using a site-specific core histone. The complete loss of canonical contacts between the N-terminal tail of H2A and DNA resulted from the remodeling while new interactions were detected between the domain and DNA approaching the center of the original nucleosome. Results are consistent with a model in which remodeling leads to the unraveling of a region of DNA from the edge of the nucleosome and to a repositioning of the H2A/H2B dimer to a noncanonical position near the center of the remodeled complex.

In mitosis, chromatin condenses into mitotic chromosomes. Transcription is inhibited. Those processes might be opposed by the chromatin remodeling of the SWI/SNF complexes. Human SWI/SNF (hSWI/SNF) complexes have been purified at different stages in the cell cycle, and hSWI/SNF was not active in cells blocked in G2-M. It appears that a transitional inactivation and reactivation of hSWI/SNF is necessary for forming of a repressed chromatin structure in mitosis and reforming of an active chromatin structure as cells go out of mitosis.

Studies were conducted to determine if a human SWI/SNF and adenosine triphosphate can create an altered nucleosomal structure that is stable in the absence of SWI/SNF. Varying preparations of hSWI/SNF complexes were utilized for the study. Results revealed the detection and characterization of the exchange between normal and altered nucleosome conformations facilitated by hSWI/SNF.

Jumonji domain-containing protein 6 (JMJD6) is a nuclear protein involved in histone modification, transcription and RNA processing. Although JMJD6 is crucial for tissue development, the link between its molecular functions and its roles in any given differentiation process is unknown. We report that JMJD6 is required for adipogenic gene expression and differentiation in a manner independent of Jumonji C domain catalytic activity. JMJD6 knockdown led to a reduction of C/EBPβ and C/EBPδ protein expression without affecting mRNA levels in the early phase of differentiation. However, ectopic expression of C/EBPβ and C/EBPδ did not rescue differentiation. Further analysis demonstrated that JMJD6 was associated with the Pparγ2 and Cebpα loci and putative enhancers. JMJD6 was previously found associated with bromodomain and extra-terminal domain (BET) proteins, which can be targeted by the bromodomain inhibitor JQ1. JQ1 treatment prevented chromatin binding of JMJD6, Pparγ2 and Cebpα expression, and adipogenic differentiation, yet had no effect on C/EBPβ and C/EBPδ expression or chromatin binding. These results indicate dual roles for JMJD6 in promoting adipogenic gene expression program by post-transcriptional regulation of C/EBPβ and C/EBPδ and direct transcriptional activation of Pparγ2 and Cebpα during adipocyte differentiation.

Investigates the mechanism of hSWI/SNF remodeling of a nucleosome. Employment of site-specific core histone-DNA cross-linking approach; Loss of canonical contacts between N-terminal tail of H2A and DNA; Non-necessity of disruption of H2A-DNA interactions in remodeling the complex.

The SWI/SNF chromatin remodeling complex facilitates gene transcription by remodeling chromatin using the energy of ATP hydrolysis. Recent studies have indicated an interplay between the SWI/SNF complex and protein-arginine methyltransferases (PRMTs). Little is known, however, about the role of SWI/SNF and PRMTs in vitamin Dreceptor (VDR)-mediated transcription. Using SWI/SNF-defective cells, we demonstrated that Brahma-related gene 1 (BRG1), an ATPase that is a component of the SWI/SNF complex, plays a fundamental role in induction by 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) of the transcription of Cyp24a1 encoding the enzyme 25-hydroxyvitamin D3 24-hydroxylase involved in the catabolism of 1,25(OH)2D3. BRG1 was found to associate with CCAAT-enhancer-binding protein (C/EBP) β and cooperate with VDR and C/EBP β in regulating Cyp24a1 transcription. PRMT5, a type II PRMT that interacts with BRG1, repressed Cyp24a1 transcription and mRNA expression. Our findings indicate the requirement of the C/EBP site for the inhibitory effect of PRMT5 via its methylation of H3R8 and H4R3. These findings indicate that the SWI/SNF complex and PRMT5 may be key factors involved in regulation of 1,25(OH)2D3 catabolism and therefore in the maintenance of calcium homeostasis by vitamin D. These studies also define epigenetic events linked to a novel mechanism of negative regulation of VDR-mediated transcription. [ABSTRACT FROM AUTHOR]

Telomeres, the safeguarding caps at the tips of chromosomes, are pivotal in the aging process of cells and have been linked to skin ailments and inflammatory conditions. Telomeres undergo a gradual reduction in length and factors such as oxidative stress hasten this diminishing process. Skin diseases including inflammatory conditions can be correlated with the shortening of telomeres and the persistent activation of DNA damage response in skin tissues. Telomere dysfunction could disrupt the balance of the skin, impairs wound healing, and may contribute to abnormal cytokine production. Skin aging and processes related to telomeres may function as one of the triggers for skin diseases. The presence of proinflammatory cytokines and dysfunctional telomeres in conditions such as Dyskeratosis Congenita implies a possible connection between the shortening of telomeres and the onset of chronic inflammatory skin disorders. In autoinflammatory skin diseases, chronic inflammation hinders wound healing thus aggravating the progression of the disease. The NF-ĸB pathway might contribute to the initiation or progression of chronic disorders by influencing mechanisms associated with telomere biology. The intricate connections between telomeres, telomerase, telomere-associated proteins, and skin diseases are still a complex puzzle to be solved. Here, we provide an overview of the impact of telomeres on both health and disease with a specific emphasis on their role in skin, inflammation and autoinflammatory skin disorders.

Autism spectrum disorder (ASD) includes a group of neurodevelopmental disorders that affect communication skills, social interaction and intellectual ability. Despite evidence suggesting a strong genetic link with ASD, the genetic determinant remains unclear. Early studies focusing on candidate genes have shown that several genes associated with neuronal synaptic function are involved in development of ASD. Linkage studies have identified several single nucleotide polymorphisms (SNPs) associated with ASD, and genome-wide association studies have implicated several loci, but failed to recognize a single specific locus with strong significance, indicating heterogeneity in ASD genetic determinants. Detection of de novo copy number variations and single nucleotide variants in several ASD probands has confirmed the genetic heterogeneity of the disease. More interestingly, next generation sequencing approaches have recently identified novel candidate genes and several point mutations in sporadic ASDs, thus increasing our knowledge of ASD etiology. The current review summarizes the findings of recent studies using genetic and genomic approaches to understand the underlying molecular mechanisms of ASD.