Abstract
The NSD1 histone methyltransferase is involved in the outgrowth disorders Sotos and Weaver syndromes and childhood acute myeloid leukemia. NSD1 is a bona fida transcriptional co-repressor for Nizp1 which is a protein including SCAN, KRAB, C2HR and zinc-finger domains. In this study the Nizp1 KRAB-domain was identified to possess an intrinsic transcriptional activation capacity suppressed in cis by the presence of the C2HR domain. Oppositely, the KRAB-domain supported C2HR domain mediated transcriptional repression. The presence of the KRAB-domain resulted in increased NSD1 co-repressor association with the C2HR domain. This study shows a new function of the KRAB-domain, C2HR-domain, and the associated factors to confer Nizp1 mediated transcriptional regulation.
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