Identification of a Ctcf cofactor, Yy1, for the X chromosome binary switch.

Abstract:

:In mammals, inactivation of one X chromosome in the female equalizes gene dosages between XX females and XY males. Two noncoding loci, Tsix and Xite, together regulate X chromosome fate by controlling homologous chromosome pairing, counting, and mutually exclusive choice. Following choice, the asymmetry of Xite and Tsix expression drives divergent chromosome fates, but how this pattern becomes established is currently unknown. Although no proven trans-acting factors have been identified, a likely candidate is Ctcf, a chromatin insulator with essential function in autosomal imprinting. Here, we search for trans-factors and identify Yy1 as a required cofactor for Ctcf. Paired Ctcf-Yy1 elements are highly clustered within the counting/choice and imprinting domain of Tsix. A deficiency of Yy1 leads to aberrant Tsix and Xist expression, resulting in a deficit of male and female embryos. Yy1 and Ctcf associate through specific protein-protein interactions and together transactivate Tsix. We propose that the Ctcf-Yy1-Tsix complex functions as a key component of the X chromosome binary switch.

journal_name

Mol Cell

journal_title

Molecular cell

authors

Donohoe ME,Zhang LF,Xu N,Shi Y,Lee JT

doi

10.1016/j.molcel.2006.11.017

subject

Has Abstract

pub_date

2007-01-12 00:00:00

pages

43-56

issue

1

eissn

1097-2765

issn

1097-4164

pii

S1097-2765(06)00788-X

journal_volume

25

pub_type

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