TY - JOUR
T1 - An ex vivo model for imprinting
T2 - Mutually exclusive binding of Cdx2 and Oct4 as a switch for imprinted and random X-inactivation
AU - Erwin, Jennifer A.
AU - del Rosario, Brian
AU - Payer, Bernhard
AU - Lee, Jeannie T.
PY - 2012/11/1
Y1 - 2012/11/1
N2 - In the early mammalian embryo, X chromosome inactivation (XCI) achieves dosage parity between males and females for X-linked genes. During mouse development, imprinted paternal XCI is observed first and switches to random XCI in the epiblast but not placental lineages. The mechanism by which this epigenetic switch occurs is currently unknown. Here, we establish an ex vivo model for imprinting and identify a novel trans-acting regulatory factor for imprinted XCI. Using an induced trophoblast stem cell (iTS) model, we show that embryonic stem (ES) cells transdifferentiated into trophoblasts retain partial memory of the XCI imprint. Cdx2, a stem cell factor that determines commitment to the extraembryonic lineage, directly binds Xist and activates expression of Xist RNA in extrembryonic cells. Cdx2 competes with Oct4, a stem cell factor that determines commitment to the embryonic lineage, for overlapping binding sites within Xist. We propose that mutually exclusive binding between Cdx2 and Oct4 in Xist underlies the switch between imprinted and random XCI in the early mouse embryo.
AB - In the early mammalian embryo, X chromosome inactivation (XCI) achieves dosage parity between males and females for X-linked genes. During mouse development, imprinted paternal XCI is observed first and switches to random XCI in the epiblast but not placental lineages. The mechanism by which this epigenetic switch occurs is currently unknown. Here, we establish an ex vivo model for imprinting and identify a novel trans-acting regulatory factor for imprinted XCI. Using an induced trophoblast stem cell (iTS) model, we show that embryonic stem (ES) cells transdifferentiated into trophoblasts retain partial memory of the XCI imprint. Cdx2, a stem cell factor that determines commitment to the extraembryonic lineage, directly binds Xist and activates expression of Xist RNA in extrembryonic cells. Cdx2 competes with Oct4, a stem cell factor that determines commitment to the embryonic lineage, for overlapping binding sites within Xist. We propose that mutually exclusive binding between Cdx2 and Oct4 in Xist underlies the switch between imprinted and random XCI in the early mouse embryo.
UR - http://www.scopus.com/inward/record.url?scp=84869056782&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84869056782&partnerID=8YFLogxK
U2 - 10.1534/genetics.112.144121
DO - 10.1534/genetics.112.144121
M3 - Article
C2 - 22942124
AN - SCOPUS:84869056782
SN - 0016-6731
VL - 192
SP - 857
EP - 868
JO - Genetics
JF - Genetics
IS - 3
ER -