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MANIPULATION OF HNF1A, HNF4A AND FOXA2 USING CRISPR-BASED MOLECULAR TOOLS SUGGEST THEIR ROLE IN REGU

Transcription factors HNF1A, HNF4A and FOXA1/2/3 regulate developmental and tissue-specific transcriptional gene networks in liver and pancreas.Alternative glycosylation affects protein structure and function, and aberrant protein glycosylation is observed in inflammation, diabetes and cancer.For instance, abnormal glucose stimulated insulin secretion in diabetes might occur through epigenetic changes in HNF1A and FOXA2, resulting in deregulation of MGAT4A, MGAT4B and MGAT5 glycosyltransferases responsible for proper glycosylaton of GLUT receptors on beta cells. In addition, HNF1A is identified by GWAS studies as a master regulator of key fucosyltransferases in liver.Following CRISPR-based manipulations, we analysed total protein glycosylation.

epigenetics, CRISPR/dCas9, glycogenes, protein glycosylation

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