DIGIT – a conserved lncRNA regulator of endoderm differentiation in embryonic stem cells

Long noncoding RNAs (lncRNAs) exhibit diverse functions, including regulation of development. Here, researchers from Massachusetts General Hospital combined genome-wide mapping of SMAD3 occupancy with expression analysis to identify lncRNAs induced by activin signaling during endoderm differentiation of human embryonic stem cells (hESCs). They found that DIGIT is divergent to Goosecoid (GSC) and expressed during endoderm differentiation. Deletion of the SMAD3-occupied enhancer proximal to DIGIT inhibits DIGIT and GSC expression and definitive endoderm differentiation. Disruption of the gene encoding DIGIT and depletion of the DIGIT transcript revealed that DIGIT is required for definitive endoderm differentiation. In addition, the researchers identified the mouse ortholog of DIGIT and showed that it is expressed during development and promotes definitive endoderm differentiation of mouse ESCs.

lncRNA

DIGIT regulates GSC in trans, and activation of endogenous GSC expression is sufficient to rescue definitive endoderm differentiation in DIGIT-deficient hESCs.

Daneshvar K, Pondick JV, Kim BM, Zhou C, York SR, Macklin JA, Abualteen A, Tan B, Sigova AA, Marcho C, Tremblay KD, Mager J, Choi MY, Mullen AC. (2016) DIGIT Is a Conserved Long Noncoding RNA that Regulates GSC Expression to Control Definitive Endoderm Differentiation of Embryonic Stem Cells. Cell Rep 17(2):353-365. [article]

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