Recognition of Histone H3K14 Acylation by MORF

Abstract

SUMMARY The monocytic leukemia zinc-finger protein-related factor (MORF) is a transcriptional coactivator and a catalytic subunit of the lysine acetyltransferase complex implicated in cancer and developmental diseases. We have previously shown that the double plant homeodomain finger (DPF) of MORF is capable of binding to acetylated histone H3. Here we demonstrate that the DPF of MORF recognizes many newly identified acylation marks. The mass spectrometry study provides comprehensive analysis of H3K14 acylation states in vitro and in vivo. The crystal structure of the MORF DPF-H3K14butyryl complex offers insight into the selectivity of this reader toward lipophilic acyllysine substrates. Together, our findings support the mechanism by which the acetyltransferase MORF promotes spreading of histone acylation.

Expanding the Reader Landscape of Histone Acylation

“…Although these studies cracked one piece of the K acyl puzzle, the Li lab has added another K acyl reader to the list with a recent report demonstrating that the DPF domains of MOZ and DPF2 are also selective readers of H3K14 acylation, notably H3K14cr (Xiong, Panchenko et al 2016). In this issue of Structure , Kutateladze and co-authors now expand our basic understanding of K acyl reading by showing that the DPF module of the MORF KAT is also a selective reader of H3K14 acylation, with a preference for H3K14Kbu (Klein, Simithy et al 2017). …”

“…Bromo, DPF and YEATS domains occur in diverse chromatin-associated proteins, including K acetyltransferases (KATs), ATP-dependent chromatin remodelers, and K methyltransferases. In this issue of Structure, Kutateladze and co-authors unveil how MORF, a double PHD-containing KAT, is a preferential reader of H3K14 acylation (Klein, Simithy et al 2017), thereby expanding our knowledge of the types of PTM landscapes reader domains interact with.…”

“…Intriguingly, Klein et al also showed that the bulkier K acyl forms (forms larger than acetylation and propionylation) are present at very low levels in vivo (Klein, Simithy et al 2017). Significantly, it has not been fully elucidated how these various acyl-CoAs end up on chromatin.…”

Histone Lysine and Genomic Targets of Histone Acetyltransferases in Mammals

“…These include bromodomains, which can bind acetylated lysines, and chromodomains and PHD domains, which can bind methylated lysines (for review see Ref. [16,17,90,91] The recruitment of MOF in alternative protein complexes have been reported. Some HAT proteins contain histone-binding domains (Table 4), KAT6A and KAT6B both have a double PHD finger domain, through which they can bind directly to modified H3K14.…”

“…Histone binding H3K14bu KAT6B DPF binds H3K14bu, Àac, Àsucc, and Àhib [91] www.advancedsciencenews.com www.bioessays-journal.com thought to acetylate H3K27. [101,102] These patterns of occupancy suggest a recruitment mechanism that applies to most transcriptionally active gene loci, rather than DNA sequence and locus-specific recruitment.…”