Unknown,Transcriptomics,Genomics,Proteomics

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Transcription profiling of mouse 3T3-MEFs derived from wild-type and SMRT RID mutants


ABSTRACT: SMRT (silencing mediator of retinoid and thyroid hormone receptors) is recruited by numerous transcription factors to mediate lineage and signal dependent transcriptional repression. We generated a knock-in mutation in the receptor interaction domain (RID) of SMRT (SMRTmRID) that solely disrupts its interaction with nuclear hormone receptors. SMRTmRID-derived 3T3-MEFs display a dramatically increased adipogenic capacity and accelerated differentiation rate. We measured global gene expression in wild-type versus SMRTmRID-derived 3T3-MEFs in the undifferentiated state to examine which pathways were altered. Our results demonstrate that SMRT-RID dependent repression is a key determinant of the adipogenic set point. Experiment Overall Design: 3T3 cells derived from wild-type and SMRT RID MEFs were cultured under pre-differentiated conditions prior to harvesting for RNA.

ORGANISM(S): Mus musculus

SUBMITTER: Ruth Yu 

PROVIDER: E-GEOD-13143 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

SMRT repression of nuclear receptors controls the adipogenic set point and metabolic homeostasis.

Nofsinger Russell R RR   Li Pingping P   Hong Suk-Hyun SH   Jonker Johan W JW   Barish Grant D GD   Ying Hao H   Cheng Sheue-Yann SY   Leblanc Mathias M   Xu Wei W   Pei Liming L   Kang Yeon-Joo YJ   Nelson Michael M   Downes Michael M   Yu Ruth T RT   Olefsky Jerrold M JM   Lee Chih-Hao CH   Evans Ronald M RM  

Proceedings of the National Academy of Sciences of the United States of America 20081209 50


The nuclear receptor corepressor, silencing mediator of retinoid and thyroid hormone receptors (SMRT), is recruited by a plethora of transcription factors to mediate lineage and signal-dependent transcriptional repression. We generated a knockin mutation in the receptor interaction domain (RID) of SMRT (SMRT(mRID)) that solely disrupts its interaction with nuclear hormone receptors (NHRs). SMRT(mRID) mice are viable and exhibit no gross developmental abnormalities, demonstrating that the reporte  ...[more]

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