TY - JOUR
T1 - Cited2, a transcriptional modulator protein, regulates metabolism in murine embryonic stem cells
AU - Li, Qiang
AU - Hakimi, Parvin
AU - Liu, Xia
AU - Yu, Wen Mei
AU - Ye, Fang
AU - Fujioka, Hisashi
AU - Raza, Syed
AU - Shankar, Eswar
AU - Tang, Fangqiang
AU - Dunwoodie, Sally L.
AU - Danielpour, David
AU - Hoppel, Charles L.
AU - Ramírez-Bergeron, Diana L.
AU - Qu, Cheng Kui
AU - Hanson, Richard W.
AU - Yang, Yu Chung
PY - 2014/1/3
Y1 - 2014/1/3
N2 - CREB-binding protein (CBP)/p300 interacting transactivator with glutamic acid (Glu) and aspartic acid (Asp)-tail 2 (Cited2) was recently shown to be essential for gluconeogenesis in the adult mouse. The metabolic function of Cited2 in mouse embryonic stem cells (mESCs) remains elusive. In the current study, the metabolism of glucose was investigated in mESCs, which contained a deletion in the gene for Cited2 (Cited2Δ/-). Compared with its parental wild type counterpart, Cited2Δ/- ESCs have enhanced glycolysis, alternations in mitochondria morphology, reduced glucose oxidation, and decreased ATP content. Cited2 is recruited to the hexokinase 1 (HK1) gene promoter to regulate transcription of HK1, which coordinates glucose metabolism in wild type ESCs. Reduced glucose oxidation and enhanced glycolytic activity in Cited2Δ/- ESCs correlates with defective differentiation during hypoxia, which is reflected in an increased expression of pluripotency marker (Oct4) and epiblast marker (Fgf5) and decreased expression of lineage specification markers (T, Gata-6, and Cdx2). Knockdown of hypoxia inducible factor-1α in Cited2Δ/- ESCs re-initiates the expression of differentiation markers T and Gata-6. Taken together, a deletion of Cited2 in mESCs results in abnormal mitochondrial morphology and impaired glucose metabolism, which correlates with a defective cell fate decision.
AB - CREB-binding protein (CBP)/p300 interacting transactivator with glutamic acid (Glu) and aspartic acid (Asp)-tail 2 (Cited2) was recently shown to be essential for gluconeogenesis in the adult mouse. The metabolic function of Cited2 in mouse embryonic stem cells (mESCs) remains elusive. In the current study, the metabolism of glucose was investigated in mESCs, which contained a deletion in the gene for Cited2 (Cited2Δ/-). Compared with its parental wild type counterpart, Cited2Δ/- ESCs have enhanced glycolysis, alternations in mitochondria morphology, reduced glucose oxidation, and decreased ATP content. Cited2 is recruited to the hexokinase 1 (HK1) gene promoter to regulate transcription of HK1, which coordinates glucose metabolism in wild type ESCs. Reduced glucose oxidation and enhanced glycolytic activity in Cited2Δ/- ESCs correlates with defective differentiation during hypoxia, which is reflected in an increased expression of pluripotency marker (Oct4) and epiblast marker (Fgf5) and decreased expression of lineage specification markers (T, Gata-6, and Cdx2). Knockdown of hypoxia inducible factor-1α in Cited2Δ/- ESCs re-initiates the expression of differentiation markers T and Gata-6. Taken together, a deletion of Cited2 in mESCs results in abnormal mitochondrial morphology and impaired glucose metabolism, which correlates with a defective cell fate decision.
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U2 - 10.1074/jbc.M113.497594
DO - 10.1074/jbc.M113.497594
M3 - Article
C2 - 24265312
AN - SCOPUS:84891687170
VL - 289
SP - 251
EP - 263
IS - 1
ER -