Essay On Hematopoiesis

Background, Aims and Objectives

The background information began providing clear explanation for hematopoiesis whereby hematopoiesis is the process of cell differentiation to blood and immune cells from multipotent hematopoietic stem cells and progenitor cells. It carried on by explaining the processes which are regulated by general RNA polymerase II transcriptional machinery and lineage specific transcriptional factors that specify the diverse cell type’s development. Then information started to come together in the direction of this study giving an overview of what this study will focus on which is Med 12 mediator. Mediators are an essential component regulating RNA polymerase II with enhancer bound regulatory factors and it exists in two major forms, the core complex and Med12-mediator. The core complex is a strong co-activator of transcription made up of 25 subunits with Med26 while Med12-mediator is able to positively and negatively control transcription. Med12 mediator has the same 25 subunits but with the addition of Med12 module that consists of Med12, Med13, CDK8 and Cyclin C. The Med12 module negatively affects transcription by inhibiting RNAP II re-initiation while Med12 positively affect transcription by interacting with SOX9 and Rta. There was an extremely detailed explanation of those individual subunits of the complex interacting specifically with different activators and repressors to regulate specific signaling pathways for example nuclear receptors interacts with Med1, MAP kinase pathway requires Med23, CDK8 interacts with myc and Med15 is required for TGFb signaling however the molecular mechanism of mediator regulatory function is not well understood. It carries on explaining the importance of Med12 in vivo pro...

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...n the genome furthermore narrowing the critical interval containing the mutation using RFLP markers and SNP analysis. Based on the knowledge about phenotype of syrah, microinjection of syr in Med12 mRNA knockdown WT mice were studied and rescued to understand the underlying genomic causes of the phenotypical effects of syr mutant zebrafish. Gene expression analysis using whole mount in situ hybridization (WISH) helped in the assessment of hematopoietic development by identifying specific mRNA species within individual cells in tissue sections, providing insights into physiological processes and disease pathogenesis. Tail snip assay of embryonic zebrafish was transected at 49 hours post fertilization to determine the residual neutrophil migration pattern in syr mutant compared to wild type mice. Many of these methods used were to further support the research finding.