Histone target selection within chromatin: an exemplary case of teamwork

Abstract

Histone modifiers like acetyltransferases, methyltransferases, and demethylases are critical regulators of most DNA-based nuclear processes, de facto controlling cell cycle progression and cell fate. These enzymes perform very precise post-translational modifications on specific histone residues, which in turn are recognized by different effector modules/proteins. We now have a better understanding of how these enzymes exhibit such specificity. As they often reside in multisubunit complexes, they use associated factors to target their substrates within chromatin structure and select specific histone mark-bearing nucleosomes. In this review, we cover the current understanding of how histone modifiers select their histone targets. We also explain how different experimental approaches can lead to conflicting results about the histone specificity and function of these enzymes.

Interaction of the Jhd2 Histone H3 Lys-4 Demethylase with Chromatin Is Controlled by Histone H2A Surfaces and Restricted by H2B Ubiquitination

“…One explanation for this apparent difference is that the in vivo interaction of Jhd2 with chromatin is probably mediated by other factors that are not present in the in vitro binding assays. Another explanation is the molecular context of the substrate used in the in vitro and in vivo assays: free histone versus chromatin, which is similar to previous reports for other chromatin modifiers (45). Because the H2A-F26A/E57A double mutation severely reduces the in vitro H2A-Jhd2 PHD finger interaction, it is conceivable that the combined mutation of H2A Phe-26 and Glu-57 residues might drastically reduce Jhd2 occupancy on chromatin at target loci.…”

Nucleosome competition reveals processive acetylation by the SAGA HAT module

“…The phenomenon of histone code "crosstalk," whereby one type of histone modification directs the establishment of another, or through which several histone modifications are recognized in tandem, has emerged as an important and widespread mechanism regulating chromatin-templated processes (5,6). The multifunctional complexes that activate transcription are thought to mediate crosstalk through "reader" domains that recognize particular chromatin marks as well as through catalytic subunits that deposit or remove histone modifications (5,7,8). As a result, distinct combinations of histone posttranslational modifications that correlate with transcriptional output cluster across the genome (9)(10)(11).…”

The Chromatin Regulator BRPF3 Preferentially Activates the HBO1 Acetyltransferase but Is Dispensable for Mouse Development and Survival

“…Results presented herein indicate that BRPF3 does not play a major role during mouse embryogenesis. In this context, it will be interesting to investigate physiological roles of JADE1 and JADE2 in vitro (8,14,23,48). It is possible that different BRPF and JADE proteins work together to mediate the action of HBO1 to maintain the H3K14ac level in vivo.…”

“…BRPF3 is paralogous to BRPF1 and BRPF2 (10, 11). These three human proteins form a subgroup within the bromodomain superfamily, within which there are 39 other members (12, 13).Several recent studies have provided insights into the molecular and biological functions of BRPF1 and BRPF2 (11,14). The bromodomain and PWWP domain of BRPF1 bind specifically to acetylated and methylated histone H3, respectively (15-18).…”

“…Several recent studies have provided insights into the molecular and biological functions of BRPF1 and BRPF2 (11,14). The bromodomain and PWWP domain of BRPF1 bind specifically to acetylated and methylated histone H3, respectively (15)(16)(17)(18).…”