N-CoR (nuclear receptor corepressor) is a corepressor for multiple transcri
ption factors including unliganded thyroid hormone receptors (TRs). In vitr
o, N-CoR can interact with the Sin3 corepressor, which in turn binds to the
histone deacetylase Rpd3 (HDAC1), predicting the existence of a corepresso
r complex containing N-CoR, Sin3, and histone deacetylase. However, previou
s biochemical studies of endogenous Sin3 complexes have failed to find an N
CoR association. Xenopus laevis eggs and oocytes contain all of the necess
ary components for transcriptional repression by unliganded TRs. In this st
udy, we report the biochemical fractionation of three novel macromolecular
complexes containing N-CoR, two of which possess histone deacetylase activi
ty, from Xenopus egg extract. One complex contains Sin3, Rpd3, and RbAp48;
the second complex contains a Sin3-independent histone deacetylase; and the
third complex lacks histone deacetylase activity. This study describes the
first biochemical isolation of endogenous N-CoR-containing HDAC complexes
and illustrates that N-CoR associates with distinct histone deacetylases th
at are both dependent and independent of Sin3. Immunoprecipitation studies
show that N-CoR binds to unliganded TR expressed in the frog oocyte, confir
ming that N-CoR complexes are involved in repression by unliganded TR. Thes
e results suggest that N-CoR targets transcriptional repression of specific
promoters through at least two distinct histone deacetylase pathways.