Identification of an enhancer that controls up-regulation of fibronectin during differentiation of embryonic stem cells into extraembryonic endoderm.
The extraembryonic endoderm is derived from inner cell mass cells of the blastocyst during early mouse embryogenesis. Formation of the extraembryonic endoderm, which later contributes to the yolk sac, appears to be a prerequisite for subsequent differentiation of the inner cell mass. While embryonic stem cells can be induced to differentiate into extraembryonic endoderm cells in vitro, the molecular mechanisms underlying this process are poorly understood. We used a promoter trap approach to search for genes that are expressed in embryonic stem cells and are highly up-regulated during differentiation to the extraembryonic endoderm fate. We showed that fibronectin fits this expression profile. Moreover we identified an enhancer in the 12th intron of the fibronectin locus that recapitulated the endogenous pattern of fibronectin expression. This enhancer carries Sox protein-binding sequences, and our analysis demonstrated that Sox7 and Sox17, which are highly expressed in the extraembryonic endoderm, were involved in enhancer activity.
Shirai
Tetsu
T
Division of Developmental Biology, Research Center for Genomic Medicine, Saitama Medical School, 1397-1 Yamane, Hidaka, Saitama 350-1241, Japan.
Miyagi
Satoru
S
Horiuchi
Daisuke
D
Okuda-Katayanagi
Tomoko
T
Nishimoto
Masazumi
M
Muramatsu
Masami
M
Sakamoto
Yoshio
Y
Nagata
Makoto
M
Hagiwara
Koichi
K
Okuda
Akihiko
A
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000502:physiology; D004622:Embryo, Mammalian / Q000166:cytology; D047108:Embryonic Development; D004707:Endoderm / Q000166:cytology*; D004742:Enhancer Elements, Genetic / Q000502:physiology*; D005353:Fibronectins / Q000235:genetics*; D020869:Gene Expression Profiling / Q000379:methods; D006609:High Mobility Group Proteins / Q000502:physiology; D007438:Introns; D051379:Mice; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D055760:SOXF Transcription Factors; D014157:Transcription Factors / Q000502:physiology; D015854:Up-Regulation
D004268:DNA-Binding Proteins; D005353:Fibronectins; D006609:High Mobility Group Proteins; D055760:SOXF Transcription Factors; C102515:Sox7 protein, mouse; D014157:Transcription Factors