Postsynthetic Modifications of Histone Primary Structure: Phosphorylation and Acetylation as Related to Chromatin Conformation and Function

Purification and characterization of a macromolecular‐translocation inhibitor III of activated glucocorticoid‐receptor‐complex binding to nuclei from rat liver

“…In the previous study [ 5 ] , we showed that histone H1, but not other histones, strongly inhibited GRC binding to DNA-cellulose. However, MTI-111 and histone H1 may be distinct molecules, because histone H1 is known to be positively charged at a physiological pH, while a MTI-111 preparation from rat liver, which was eluted with 0.3 M NaCl from a DEAE-cellulose column [13,141, may be negatively charged, and it has a higher molecular mass (69 kDa) than histone H1 (21 kDa) [26]. Furthermore, MTI-I11 acts by interaction with the activated GRC, but not with DNA, and in contrast to this histone H1 binds to DNA as a masking protein without interaction with the receptor [5, 241. Unligandedhnactivated glucocorticoid receptor (a 9 S form) has been reported to consist of a single steroid-binding protein (98 kDa) [27, 281 and a dimer of 90-kDa heat shock protein (hsp 90) [27, 281.…”

The Action of Growth and Developmental Hormones

“…Thus, posttranslational modifications of histones, such as phosphorylation, acetylation, and ADP-ribosylation, appear to accompany changes in the nucleosomal organization of chromatin and alterations in its template activity, including those induced by some hormones (Libby, 1973;Allfrey, 1977;Davie and Candido, 1978;Johnson and Allfrey, 1978;Mathis et at., 1978Mathis et at., , 1980Vidali et at., 1978;Samuels et at., 1980). The nonhistone "high mobility group" (HMG) proteins have also attracted attention, since a subset of these seems to mediate globin gene sensitivity to DNase I in isolated chromatin (Goodwin et at., 1978;Weisbrod and Weintraub, 1979).…”

The Action of Growth and Developmental Hormones

“…Many workers now believe that conformational changes in chromosomal organization that facilitate gene transcription may be mediated via a redistribution of newly made non-histone chromosomal proteins or the post-translational modifications of these proteins as well as of histones, i.e. phosphorylation, acetylation and ADPribosylation (see Bradbury & Javaherian, 1977;Johnson & Allfrey, 1978). However, the extreme complexity of these proteins and the lack of any good evidence for their precise role in regulating gene expression have turned out to be major handicaps.…”

“…More recently, post-translational modifications of histones, particularly histone H I , such as phosphorylation and acetylation have been found to cause a change in the nucleosomal organization of chromatin, thus altering its template activity and susceptibility to nuclease digestion. There is evidence already that some hormones known to affect transcriptional activity also bring about such post-translational modifications of histones and non-histone proteins (Johnson & Allfrey, 1978). Whereas it can be easily predicted that such studies will multiply in the near future, it is difficult to predict how soon we shall fully understand, in the context of hormone action, the meaning of such changes in the organization of chromatin or posttranslational modification of chromosomal proteins.…”

“…Thus, for example, the balance between Na+ and K+ ions seems to be critical for the organization and function of chromosomes (Kroeger & Lezzi, 1966;Kaplan, 1978). Transcription of genes is also now turning out to be closely linked to acetylation and phosphorylation of histones and non-histone proteins (Allfrey, 1977; see Botchan & Watson, 1978; Johnson & Allfrey, 1978). As a relatively late response, the selective stabilization and degradation of hormone-induced messengers is an important aspect of hormonal amplification of translation of specifically induced mRNA.…”