In eucaryotes, genes are packed within chromatin. Formation of nucleosomes and higher order chromatin structures can render the DNA inaccessible to transcription factors and RNA polymerases. The repressive chromatin structure must be remodeled to allow transcription to occur. Two classes of chromatin-remodeling complexes have been discovered: one, histone acetyltransferase and deacetylases which covalently modify histones by adding or removing an acetyl group from histone tails; two, the ATP-dependent remodeling complexes which use the energy of ATP to disrupt nucleosome structures. Before our study, it was generally believed that ATP-dependent complexes are only involved in gene activation by making DNA more accessible to transcription activators. In this work, we have purified a new human complex, named NURD, which contains both ATP-dependent nucleosome disruption activity and histone deacetylase activity (which is usually associated withtranscriptional repression). The deacetylase activity is stimulated by ATP on nucleosomal templates, suggesting that in this instance nucleosome disruption helps the deacetylase to access its substrates (Molecular Cell 2:851, 1998). In addition, one subunit of NURD was identified as MTA1, a metastasis-associated protein with a region similar to the nuclear receptor corepressor, N-CoR; and antibodies against NURD partially relieve transcriptional repression mediated by thyroid hormone receptor. Our results demonstrate that ATP- dependent chromatin-remodeling can participate in transcriptional repression by assisting repressors in gaining access to chromatin. - Chromatin, NURD, CHD, histone deacetylase, transcription, Cancer
