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B10 - Joost Gribnau:

Epigenetic mechanisms in X chromosome inactivation

X chromosome inactivation (XCI) involves multiple layers of epigenetic modifications and provides a powerful model system to study gene regulation. XCI is mediated by cis-accumulation of the X-encoded long noncoding RNA, Xist. The molecular mechanism by which Xist inactivates one entire X chromosome remains unresolved. Recently, Xist interactor screens identified several new factors, including SPEN. These studies implicate SPEN in the initiation of XCI, where it is proposed to cooperate with HDAC3, PRC1 and PRC2. With this proposal we aim to develop and apply new assays to define the role of SPEN and to unravel the complex interplay of epigenetic modifications and chromatin modifying enzymes during initiation of XCI.

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