Kornblihtt indicates that diverse splicing factors associate with a carboxy terminal domain (CTD) of RNAPII [ 47], whereas phosphorylated CTD of RNAPII can recruit Histone-lysine N-methyltransferase SETD2, which modulates the histone modification H3K36me3 [ 48].
Chromatin structure influences splicing choices but splicing can also actively modulate the pattern of histone modification in chromatin.
Correspondingly, many small molecule compounds have been designed to modulate the activity of histone demethylases and DNA methyltransferases, and some of them have been developed into therapeutic drugs or put into clinical trials.
miR-24 has been reported to modulate the expression of histone H2AX [29], which is a key component in the repair of DNA double-strand breaks.
Thus, USP7 might in addition modulate the ubiquitination status of histone H3 and thereby regulate DNMT1 association with chromatin.
Recent data suggest that this drug can modulate the epigenome by inhibiting histone deacetylases and activating the expression of methylated genes by stimulating active, replication-independent demethylation (Detich et al., 2003).
Post-translation modifications of histones modulate the accessibility and transcriptional competence of specific chromatin regions within the eukaryotic genome.
Acetylation/deacetylation of lysine residues is one of the post-translational modifications that modulate the function of proteins as histones and non-histone proteins such as the transcription factor GATA1, the chaperone HSP90, tubulin and p53.
In summary these data indicate that combinatorial phosphorylation and acetylation of histone H3 modulate the affinity for readers and potentially also for erasers.
The discovery of nuclear histone acetyltransferases (HATs) in the mid nineties has literally opened a new field of investigation into post-translational modifications that target histones and modulate the chromatin state either locally or over large genomic loci.
