Joint Binding of OTX2 and MYC in Promotor Regions Is Associated with High Gene Expression in Medulloblastoma

Both OTX2 and MYC are important oncogenes in medulloblastoma, the most common malignant brain tumor in childhood. Much is known about MYC binding to promoter regions, but OTX2 binding is hardly investigated. We used ChIP-on-chip data to analyze the binding patterns of both transcription factors in D425 medulloblastoma cells. When combining the data for all promoter regions in the genome, OTX2 binding showed a remarkable bi-modal distribution pattern with peaks around −250 bp upstream and +650 bp downstream of the transcription start sites (TSSs). Indeed, 40.2% of all OTX2-bound TSSs had more than one significant OTX2-binding peak. This OTX2-binding pattern was very different from the TSS-centered single peak binding pattern observed for MYC and other known transcription factors. However, in individual promoter regions, OTX2 and MYC have a strong tendency to bind in proximity of each other. OTX2-binding sequences are depleted near TSSs in the genome, providing an explanation for the observed bi-modal distribution of OTX2 binding. This contrasts to the enrichment of E-box sequences at TSSs. Both OTX2 and MYC binding independently correlated with higher gene expression. Interestingly, genes of promoter regions with multiple OTX2 binding as well as MYC binding showed the highest expression levels in D425 cells and in primary medulloblastomas. Genes within this class of promoter regions were enriched for medulloblastoma and stem cell specific genes. Our data suggest an important functional interaction between OTX2 and MYC in regulating gene expression in medulloblastoma

HCI design for people with visual disability in social interaction

In the Human Computer Interaction (HCI) field, it has been a long tradition of concern of accessing computer systems by people with visual impairments. It is important to develop high quality user interfaces, accessible, usable, and desirable for these people. In this paper, we first report a preliminary background review about HCI design for people with visual disability. The review of the problems in social interaction the blind people may encounter, are also presented. Further, we narrow down our research scope and focus on gaze and eye contact, which have important social meaning in face-to-face communication. We then identify our research objective that is to design gaze simulation for people with visual impairments. Finally, we report the prototypes of our research project and the progress made so far

Visual Impairment

The past decade has witnessed a considerable upsurge of clinical and research interest in the problems of developmentally and physically the fields of psychology, disabled persons. Indeed, professionals from special education, rehabilitation, psychiatry, and social work have all directed attention to the development and implementation of evaluation and remedial programs. The heightened activity in this area is in part a result of early assessment research with these populations, which provided preliminary evidence of difficulties in social and emotional adjustment in many disabled individuals. In response to these findings, many intervention efforts have been implemented to deal with these issues and improve the life situation of the disabled. Also, there were indications that developmentally and physically disabled children often were deprived of adequate educations. As a result, legal and legislative initiatives have been enacted in recent years to make public education available to all students irrespective of disability. Central to all therapeutic and psychoeducational endeavors with the disabled is psychological evaluation. Only through careful and com­prehensive psychological evaluation can areas of deficit as well as strengths be identified. Once treatment targets and goals have been ascertained, psychological evaluation is needed to determine the efficacy of intervention strategies. However, the field of psychological evalua­tion, in general, and with disabled persons, in particular, has become highly specialized. This is largely a function of the changing roles of psychological evaluators.https://nsuworks.nova.edu/cps_facbooks/1221/thumbnail.jp

OTX2 sustains a bivalent-like state of OTX2-bound promoters in medulloblastoma by maintaining their H3K27me3 levels

Recent studies showed frequent mutations in histone H3 lysine 27 (H3K27) demethylases in medulloblastomas of Group 3 and Group 4, suggesting a role for H3K27 methylation in these tumors. Indeed, trimethylated H3K27 (H3K27me3) levels were shown to be higher in Group 3 and 4 tumors compared to WNT and SHH medulloblastomas, also in tumors without detectable mutations in demethylases. Here, we report that polycomb genes, required for H3K27 methylation, are consistently upregulated in Group 3 and 4 tumors. These tumors show high expression of the homeobox transcription factor OTX2. Silencing of OTX2 in D425 medulloblastoma cells resulted in downregulation of polycomb genes such as EZH2, EED, SUZ12 and RBBP4 and upregulation of H3K27 demethylases KDM6A, KDM6B, JARID2 and KDM7A. This was accompanied by decreased H3K27me3 and increased H3K27me1 levels in promoter regions. Strikingly, the decrease of H3K27me3 was most prominent in promoters that bind OTX2. OTX2-bound promoters showed high levels of the H3K4me3 and H3K9ac activation marks and intermediate levels of the H3K27me3 inactivation mark, reminiscent of a bivalent modification. After silencing of OTX2, H3K27me3 levels strongly dropped, but H3K4me3 and H3K9ac levels remained high. OTX2-bound bivalent genes showed high expression levels in D425, but the expression of most of these genes did not change after OTX2 silencing and loss of the H3K27me3 mark. Maintaining promoters in a bivalent state by sustaining H3K27 trimethylation therefore seems to be an important function of OTX2 in medulloblastoma, while other transcription factors might regulate the actual expression levels of these genes