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Yingqun Huang

My lab is interested in the molecular mechanisms of the long noncoding RNA (lncRNA) H19 in the regulation of gene expression. H19 is encoded by the developmentally regulated imprinted H19 gene, which, together with its co-regulated Igf2, plays important roles in embryo development and growth control. Two human genetic disorders have been linked to the H19-Igf2 locus: Silver-Russell Syndrome and Beckwith-Wiedemann Syndrome. H19 is highly expressed in human and mouse placentas and fetal tissues as well as in a subset of adult tissues including skeletal muscle, heart, haematopoietic stem cells, and endometrium. In addition, aberrant H19 expression has been detected in diverse human malignancies. H19 is a multifunctional lncRNA that has activities both in the nucleus and in the cytoplasm. We have previously reported that H19 acts as a molecular sponge for microRNA let-7, contributing to regulation of muscle differentiation, tumor metastasis, and endometrium development. We have also reported that H19 positively controls skeletal muscle cell insulin sensitivity by reducing the bioavailability of let-7. Recently, we discover yet another new function of H19: it regulates DNA methylation genome wide by modulating the activity of S-adenosylhomocysteine hydrolase (SAHH). H19 binds to SAHH and inhibits its function. SAHH is the only mammalian enzyme capable of hydrolyzing S-adenosylhomocysteine (SAH), which is a potent feedback inhibitor of SAM-dependent methyltransferases that methylate diverse cellular components, including DNA, RNA, proteins, lipids, and neurotransmitters. We propose that this novel epigenetic regulatory mechanism may underlie the DNA methylation dynamics associated with development and diseases and that this mode of regulation may extend to other cellular components. Currently, our research centers on the mechanistic understanding of H19 in endocrine disorders including type-2 diabetes and infertility, in addition to reproductive tract cancers, with the ultimate goal of discovering new molecular signatures and pathways for preventing and treating these diseases.