Active genes are tri-methylated at K4 of histone H3

Lysine methylation of histones in vivo occurs in three states: mono-, di- and tri-methyl. Histone H3 has been found to be di-methylated at lysine 4 (K4) in active euchromatic regions but not in silent heterochromatic sites. Here we show that the Saccharomyces cerevisiae Set1 protein can catalyse di- and tri-methylation of K4 and stimulate the activity of many genes. Using antibodies that discriminate between the di- and tri-methylated state of K4 we show that di-methylation occurs at both inactive and active euchromatic genes, whereas tri-methylation is present exclusively at active genes. It is therefore the presence of a tri-methylated K4 that defines an active state of gene expression. These findings establish the concept of methyl status as a determinant for gene activity and thus extend considerably the complexity of histone modifications.     

Structural alteration of hair cells in the contralateral ear resulting from extracochlear electrical stimulation

Chronic electrical stimulation of the auditory nerve in patients with profound sensori-neural deafness is becoming increasingly routine. Therefore, it is important to understand more about the long-term consequences of this procedure. Hitherto, structural studies in animals after electrocochlear stimulation have concentrated on the stimulated cochlea. Here we have examined the effects of unilateral extracochlear electrical stimulation on the spiral organ of both the ipsilateral and contralateral ears of the mature guinea pig, and have found alterations in the structure of the outer hair cells and their efferent nerve terminals in the contralateral as well as the ipsilateral cochlea. This is the first evidence for a structural influence of efferent activity on the cochlea. Although the importance of the efferent system, consisting of the crossed and uncrossed olivo-cochlear bundles, is well established in providing central control of the sensory pathways, its exact role in hearing is incompletely understood. However, it is known that the outer hair cells and their efferent innervation are important in their contribution to inner hair cell responses and in modulating the micromechanics of the whole cochlea. These efferent functions now appear to be related to an important part of cochlear morphology, and are also relevant to our understanding of cochlear neurobiology, normal development and the management of hearing disability in both adult and child.     

The binding of copper in human ceruloplasmin

Zusammenfassung Mit Photooxydation und Diazotierung wird gezeigt, dass Histidinreste an der Bindung von Kupfer an Caeruloplasmin beteiligt sind.