Early embryonic lethality of mice with disrupted transcription cofactor PIMT/NCOA6IP/Tgs1 gene.
Early embryonic lethality of mice with disrupted transcription cofactor PIMT/NCOA6IP/Tgs1 gene.
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DOI:
10.1016/j.mod.2012.08.002
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发表时间:
2012-09
影响因子:
2.6
通讯作者:
Reddy, Janardan K.
中科院分区:
文献类型:
--
作者:
Jia, Yuzhi;Viswakarma, Navin;Crawford, Susan E.;Sarkar, Joy;Rao, M. Sambasiva;Karpus, William J.;Kanwar, Yashpal S.;Zhu, Yi-Jun;Reddy, Janardan K.
PIMT (also known as PIPMT/NCOA6IP/Tgs1), first isolated as a transcription coactivator PRIP (NCOA6)-interacting 96-kDa protein with RNA-binding property, possesses RNA methyltransferase activity. As a transcription coactivator binding protein, PIMT enhances the nuclear receptor transcriptional activity and its methyltransferase property is involved in the formation of the 2,2,7-trimethylguanosine cap of non-coding small RNAs, but the in vivo functions of this gene have not been fully explored. To elucidate the biological functions, we used gene targeting to generate mice with a disrupted PIMT/Tgs1 gene. Disruption of PIMT gene results in early embryonic lethality due to impairment of development around the blastocyst and uterine implantation stages. We show that PIMT is expressed in all cells of the E3.5 day blastocyst in the mouse. PIMT null mutation abolished PIMT expression in all cells of the blastocyst and caused a reduction in the expression of Oct4 and Nanog transcription factor proteins in the E3.5 blastocyst resulting in the near failure to form inner cell mass (ICM). With conditional deletion of PIMT gene, mouse embryonic fibroblasts (MEFs) exhibit defective wound healing in the scratch assay and a reduction in cell proliferation due to decreased G0/G1 transition and G2/M phase cell cycle arrest. We conclude that PIMT/NCOA6IP, which is expressed in all cells of the 3.5 day stage blastocyst, is indispensable for early embryonic development.
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影响因子:
64.5
作者:
Mitsui, K;Tokuzawa, Y;Yamanaka, S
通讯作者:
Yamanaka, S
影响因子:
11.8
作者:
Chazaud, Claire;Yamanaka, Yojiro;Rossant, Janet
通讯作者:
Rossant, Janet
影响因子:
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作者:
Brykailo, Melissa A.;Corbett, Anita H.;Fridovich-Keil, Judith L.
通讯作者:
Fridovich-Keil, Judith L.
DOI:
10.1016/s0006-291x(03)01514-6
发表时间:
2003-09-12
影响因子:
3.1
作者:
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通讯作者:
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影响因子:
5.3
作者:
Fortschegger, Klaus;Wagner, Bettina;Grillari, Johannes
通讯作者:
Grillari, Johannes