Pathway description:
Chromatin is the substance which becomes visible chromosomes during cell division. Its basic unit is nucleosome, composed of 146 bp DNA and eight histone proteins. The structure of chromatin is dynamically changing, at least in part, depending on the need of transcription. In the metaphase of cell division, the chromatin is condensed into the visible chromosome.
Transcription is the process through which a DNA sequence is enzymatically copied by an RNA polymerase to produce a complementary RNA. In eukaryotes, it takes place in the nucleus, mitochondria and chloroplast.
Protein acetylation plays a crucial role in regulating chromatin structure and transcriptional activity. Acetylation complexes or deacetylation complexes can be recruited to DNA-bound transcription factors (TFs) in response to signaling pathways. Histone hyperacetylation by histone acetyltransferases (HATs) is associated with transcriptional activation, presumably by remodeling nucleosomal structure into an open conformation more accessible to transcription complexes. Conversely, histone deacetylation by deacetylation complexes (such as HDAC) is associated with transcriptional repression reversing the chromatin remodeling process.Several transcriptional coactivators and corepressors possess intrinsic acetylase or deacetylase enzymatic activities, respectively. Site-specific acetylation of a growing list of non-histone proteins, including p53 and E2F, has been shown to play an important role in transcriptional regulation and cell proliferation.
Selected Reviews:
Davie JR, Samuel SK, Spencer VA, et al. (1999)Organization of chromatin in cancer cells: role of signalling pathways. Biochem Cell Biol.77(4):265-75.
Davie JR, Samuel SK, Spencer VA, et al. (1999)Organization of chromatin in cancer cells: role of signalling pathways. Biochem Cell Biol.77(4):265-75.
Spencer VA, Davie JR.(2000)Signal transduction pathways and chromatin structure in cancer cells. J Cell Biochem Suppl. 35:27-35.
Crosio C, Heitz E, Allis CD,et al. (2003)Chromatin remodeling and neuronal response: multiple signaling pathways induce specific histone H3 modifications and early gene expression in hippocampal neurons. J Cell Sci. 116(Pt 24):4905-14.
