Novel CTCF binding at a site in exon1A of BCL6 is associated with active histone marks and a transcriptionally active locus

BCL6 is a zinc-finger transcriptional repressor, which is highly expressed in germinal centre B-cells and is essential for germinal centre formation and T-dependent antibody responses. Constitutive BCL6 expression is sufficient to produce lymphomas in mice. Deregulated expression of BCL6 due to chromosomal rearrangements, mutations of a negative autoregulatory site in the BCL6 promoter region and aberrant post-translational modifications have been detected in a number of human lymphomas. Tight lineage and temporal regulation of BCL6 is, therefore, required for normal immunity, and abnormal regulation occurs in lymphomas. CCCTC-binding factor (CTCF) is a multi-functional chromatin regulator, which has recently been shown to bind in a methylation-sensitive manner to sites within the BCL6 first intron. We demonstrate a novel CTCF-binding site in BCL6 exon1A within a potential CpG island, which is unmethylated both in cell lines and in primary lymphoma samples. CTCF binding, which was found in BCL6-expressing cell lines, correlated with the presence of histone variant H2A.Z and active histone marks, suggesting that CTCF induces chromatin modification at a transcriptionally active BCL6 locus. CTCF binding to exon1A was required to maintain BCL6 expression in germinal centre cells by avoiding BCL6-negative autoregulation. Silencing of CTCF in BCL6-expressing cells reduced BCL6 mRNA and protein expression, which is sufficient to induce B-cell terminal differentiation toward plasma cells. Moreover, lack of CTCF binding to exon1A shifts the BCL6 local chromatin from an active to a repressive state. This work demonstrates that, in contexts in which BCL6 is expressed, CTCF binding to BCL6 exon1A associates with epigenetic modifications indicative of transcriptionally open chromatin

Production System waste reduction using Value stream mapping : An Industrial case study

The rapid rise in global population and market demands have mandated industries to introduce better and quality products to meet up their rushing needs. However, achiev-ing such goals need optimal production system and robust strategies. Exploring in depth it can be visualized that most of the manufacturing set ups suffers losses or relatively lower benefits due to improper and high wastages. Hence it is very important for man-ufacturing industries to explore the techniques which help them to improve their pro-duction system. The key techniques from Lean Manufacturing (LM) such as Value Stream Mapping (VSM) and Ishikawa diagram were explored in this work for enhanc-ing production capacity, reducing rework, reducing wastages and arriving to a well-defined optimal process flow which in turn help in achieving higher productivity. How-ever, the implementation of Lean and Value stream mapping depends on the production scale and has its own significance to different manufacturing setup. With that motive, in this thesis work the emphasis was made on exploring VSM technique for better pro-duction optimization in manufacturing sector

Novel stereospecific synthesis of (-) (2s, 3s)-1-dimethylamino-3-(3-methoxyphenyl)-2-methyl pentan-3-ol

The present invention relates to a novel stereospecific synthesis of (−)(2S,3S)-1-dimethylamino-3-(3-methoxyphenyl)-2-methyl pentan-3-ol an intermediate in the synthesis of 3-[(1R,2R)-3-(dimethylamino)-1-ethyl-2-methylpropyl]pheno