The globin genes can be enriched about a thousand fold in the form of nuclease-resistant DNA-nonhistone protein complex from the chicken reticulocyte and erythrocyte nuclei but not from oviduct nuclei. Preliminary results suggest that 30-50% of the coding region of the alpha and beta globin genes are bound by nonhistone proteins in the reticulocyte and erythrocyte nuclei presumably by the association of the globin gene around one or more of nonhistone protein(s). 9S globin gene-protein complex has been isolated from reticulocytes. It is possible that nonhistone proteins are bound to the regions flanking the coding region of the globin genes as well as the intervening sequences. (a) With the use of cloned structural alpha and beta globin genes we like to map the non-histone protein binding sites in the globin genes in both reticulocytes and erythrocytes, and the possible changes in the binding of nonhistone proteins to embryonic and adult globin genes will be investigated. (b) The mode of binding of the nonhistone proteins to the globin genes in the 9S gene-protein complex will be investigated. (c) The globin gene-specific proteins will be isolated by the globin gene-cellulose affinity chromatography. (d) The possible effect of the gene-specific nonhistone proteins on the transcription of the globin genes and DNase I sensitivity of the gene in reconstituted chromatin will be investigated. (e) We like to attempt to isolate other gene-nonhistone protein complexes including tumor virus genes in transformed cells. (f) The possible association of active genes to nuclear matrix will be investigated. (g) The possible tissue-specific modification of globin gene bases and its effect on protein-binding will be tested.