The new dimension of endocrinology: nuclear/intracellular endocrinology.

sideration as DNA methylation patterns may be reversible and changeable under certain physiological and pathological conditions. This idea is supported by the fact that differentiated cells are still potent enough to be converted into iPS cells, presumably coupling with altered DNA methylation pattern. Beyond canonical epigenomic modification, the current view of the epigenome includes histone modifications. Many types of post-translation modifications have been recorded on the N-terminal ends of histones. The combination of histone modifications is assumed to direct the chromatin state, and this assumption is proposed as a theory designated as the “histone code” (in 1999). Histone acetylation was firstly found in 1995 to be closely related with the state of activated chromatin like euchromatin. Indeed enzymes such as p300/CBP to acetylate histones are known to co-activate the transactivation function of DNA-binding transcription factors, while histone deacetylases (HDACs) serve as transcriptional co-repressors through histone inactivation by histone deacetylation. Similar analyses have been performed to characterize histone modifications and their responsible enzymes, and basically could verify the hypothesis of the “histone code.” Among the histone modifications, histone methylation has emerged as the most upstream and critical histone mark directing the chromatic state, but appears unlikely to resemble histone acetlylation. Histone H3 lysine 4 and 36 methylations (H3K4 and H3K36) activate the chromatin state, while histone inactivation such as heterochromatin is induced by methylations of H3K9 and H3K27. Dependent on the lysine residues on histone N-tails, histone methylation leads in the opposite direction. Besides such well-documented modifications, unknown modifications on histones are still The New Dimension of Endocrinology: Nuclear/Intracellular Endocrinology