title: Bright/Arid3A acts as a barrier to somatic cell reprogramming through direct regulation of Oct4, Sox2, and Nanog.
abstract: We show here that singular loss of the Bright/Arid3A transcription factor leads to reprograming of mouse embryonic fibroblasts (MEFs) and enhancement of standard four-factor (4F) reprogramming. Bright-deficient MEFs bypass senescence and, under standard embryonic stem cell (ESC) culture conditions, spontaneously form clones that in vitro express pluripotency markers, differentiate to all germ lineages, and in vivo form teratomas and chimeric mice. We demonstrate that BRIGHT binds directly to the promoter/enhancer regions of Oct4, Sox2, and Nanog to contribute to their repression in both MEFs and ESCs. Thus, elimination of the BRIGHT barrier may provide an approach for somatic cell reprogramming.
authors: Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, TX 78712, USA.
authors: Melissa
authors: M
authors: Popowski
authors: Immunobiology and Cancer Program, Oklahoma Medical Research Foundation, Departments of Cell Biology and Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
authors: Troy D
authors: TD
authors: Templeton
authors: Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, TX 78712, USA.
authors: Bum-Kyu
authors: BK
authors: Lee
authors: Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, TX 78712, USA.
authors: Catherine
authors: C
authors: Rhee
authors: Immunobiology and Cancer Program, Oklahoma Medical Research Foundation, Departments of Cell Biology and Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
authors: He
authors: H
authors: Li
authors: Immunobiology and Cancer Program, Oklahoma Medical Research Foundation, Departments of Cell Biology and Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
authors: Cathrine
authors: C
authors: Miner
authors: Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, TX 78712, USA.
authors: Joseph D
authors: JD
authors: Dekker
authors: Department of Developmental Biology and Cancer Research, The Hebrew University Medical School, Jerusalem 91120, Israel.
authors: Shari
authors: S
authors: Orlanski
authors: Department of Developmental Biology and Cancer Research, The Hebrew University Medical School, Jerusalem 91120, Israel.
authors: Yehudit
authors: Y
authors: Bergman
authors: Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, TX 78712, USA.
authors: Vishwanath R
authors: VR
authors: Iyer
authors: Immunobiology and Cancer Program, Oklahoma Medical Research Foundation, Departments of Cell Biology and Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
authors: Carol F
authors: CF
authors: Webb
authors: Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, TX 78712, USA.
authors: Haley
authors: H
authors: Tucker
mesh_terms: D000818:Animals; D002460:Cell Line; D065150:Cellular Reprogramming; D016922:Cellular Senescence; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D016256:Lewis X Antigen / Q000378:metabolism; D051379:Mice; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D059467:Transcriptome
chemical_list: C097532:Arid3a protein, mouse; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D016256:Lewis X Antigen; D000071317:Nanog Homeobox Protein; C475540:Nanog protein, mouse; D050814:Octamer Transcription Factor-3; D034741:RNA, Small Interfering; D055748:SOXB1 Transcription Factors; D014157:Transcription Factors