New Twists of a TAIL: Novel Insights into the Histone Binding Properties of a Highly Conserved PHD Finger Cluster Within the MLR Family of H3K4 Mono-methyltransferases

Overview

Journal Nucleic Acids Res

Publisher Oxford University Press

Specialty Biochemistry

Date 2023 Aug 28

PMID 37638761

Authors

Claudia B Zraly

Richard Schultz

Manuel O Diaz

Andrew K Dingwall

Affiliations

Soon will be listed here.

Abstract

Enhancer activation by the MLR family of H3K4 mono-methyltransferases requires proper recognition of histones for the deposition of the mono-methyl mark. MLR proteins contain two clusters of PHD zinc finger domains implicated in chromatin regulation. The second cluster is the most highly conserved, preserved as an ancient three finger functional unit throughout evolution. Studies of the isolated 3rd PHD finger within this cluster suggested specificity for the H4 [aa16-20] tail region. We determined the histone binding properties of the full three PHD finger cluster b module (PHDb) from the Drosophila Cmi protein which revealed unexpected recognition of an extended region of H3. Importantly, the zinc finger spacer separating the first two PHDb fingers from the third is critical for proper alignment and coordination among fingers for maximal histone engagement. Human homologs, MLL3 and MLL4, also show conservation of H3 binding, expanding current views of histone recognition for this class of proteins. We further implicate chromatin remodeling by the SWI/SNF complex as a possible mechanism for the accessibility of PHDb to globular regions of histone H3 beyond the tail region. Our results suggest a two-tail histone recognition mechanism by the conserved PHDb domain involving a flexible hinge to promote interdomain coordination.

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References

Fitts R, Reuveny Z, van Amsterdam J, Mulholland J, Botstein D . Substitution of tyrosine for either cysteine in beta-lactamase prevents release from the membrane during secretion. Proc Natl Acad Sci U S A. 1987; 84(23):8540-3. PMC: 299580. DOI: 10.1073/pnas.84.23.8540. View

Lavigne M, Eskeland R, Azebi S, Saint-Andre V, Jang S, Batsche E . Interaction of HP1 and Brg1/Brm with the globular domain of histone H3 is required for HP1-mediated repression. PLoS Genet. 2009; 5(12):e1000769. PMC: 2782133. DOI: 10.1371/journal.pgen.1000769. View

Marenda D, Zraly C, Dingwall A . The Drosophila Brahma (SWI/SNF) chromatin remodeling complex exhibits cell-type specific activation and repression functions. Dev Biol. 2004; 267(2):279-93. DOI: 10.1016/j.ydbio.2003.10.040. View

Dingwall A, Beek S, McCALLUM C, Tamkun J, Kalpana G, Goff S . The Drosophila snr1 and brm proteins are related to yeast SWI/SNF proteins and are components of a large protein complex. Mol Biol Cell. 1995; 6(7):777-91. PMC: 301240. DOI: 10.1091/mbc.6.7.777. View

Zheng S, Bi Y, Chen H, Gong B, Jia S, Li H . Molecular basis for bipartite recognition of histone H3 by the PZP domain of PHF14. Nucleic Acids Res. 2021; 49(15):8961-8973. PMC: 8421203. DOI: 10.1093/nar/gkab670. View

Jain K, Fraser C, Marunde M, Parker M, Sagum C, Burg J . Characterization of the plant homeodomain (PHD) reader family for their histone tail interactions. Epigenetics Chromatin. 2020; 13(1):3. PMC: 6979384. DOI: 10.1186/s13072-020-0328-z. View

Zeng L, Zhang Q, Li S, Plotnikov A, Walsh M, Zhou M . Mechanism and regulation of acetylated histone binding by the tandem PHD finger of DPF3b. Nature. 2010; 466(7303):258-62. PMC: 2901902. DOI: 10.1038/nature09139. View

Dreveny I, Deeves S, Fulton J, Yue B, Messmer M, Bhattacharya A . The double PHD finger domain of MOZ/MYST3 induces α-helical structure of the histone H3 tail to facilitate acetylation and methylation sampling and modification. Nucleic Acids Res. 2013; 42(2):822-35. PMC: 3902925. DOI: 10.1093/nar/gkt931. View

Armstrong J, Papoulas O, Daubresse G, Sperling A, Lis J, Scott M . The Drosophila BRM complex facilitates global transcription by RNA polymerase II. EMBO J. 2002; 21(19):5245-54. PMC: 129039. DOI: 10.1093/emboj/cdf517. View

10.

Zraly C, Marenda D, Nanchal R, Cavalli G, Muchardt C, Dingwall A . SNR1 is an essential subunit in a subset of Drosophila brm complexes, targeting specific functions during development. Dev Biol. 2003; 253(2):291-308. DOI: 10.1016/s0012-1606(02)00011-8. View

11.

Musselman C, Kutateladze T . Handpicking epigenetic marks with PHD fingers. Nucleic Acids Res. 2011; 39(21):9061-71. PMC: 3241642. DOI: 10.1093/nar/gkr613. View

12.

Ruff K, Pappu R . AlphaFold and Implications for Intrinsically Disordered Proteins. J Mol Biol. 2021; 433(20):167208. DOI: 10.1016/j.jmb.2021.167208. View

13.

Gatchalian J, Wang X, Ikebe J, Cox K, Tencer A, Zhang Y . Accessibility of the histone H3 tail in the nucleosome for binding of paired readers. Nat Commun. 2017; 8(1):1489. PMC: 5686127. DOI: 10.1038/s41467-017-01598-x. View

14.

Elfring L, Daniel C, Papoulas O, Deuring R, Sarte M, MOSELEY S . Genetic analysis of brahma: the Drosophila homolog of the yeast chromatin remodeling factor SWI2/SNF2. Genetics. 1998; 148(1):251-65. PMC: 1459776. DOI: 10.1093/genetics/148.1.251. View

15.

Xu F, Zhang K, Grunstein M . Acetylation in histone H3 globular domain regulates gene expression in yeast. Cell. 2005; 121(3):375-85. DOI: 10.1016/j.cell.2005.03.011. View

16.

Sharma R, Zhou M . Partners in crime: The role of tandem modules in gene transcription. Protein Sci. 2015; 24(9):1347-59. PMC: 4570530. DOI: 10.1002/pro.2711. View

17.

Li W, Zhao A, Tempel W, Loppnau P, Liu Y . Crystal structure of DPF3b in complex with an acetylated histone peptide. J Struct Biol. 2016; 195(3):365-372. DOI: 10.1016/j.jsb.2016.07.001. View

18.

Zheng W, Zhang C, Li Y, Pearce R, Bell E, Zhang Y . Folding non-homologous proteins by coupling deep-learning contact maps with I-TASSER assembly simulations. Cell Rep Methods. 2021; 1(3). PMC: 8336924. DOI: 10.1016/j.crmeth.2021.100014. View

19.

Sanchez R, Zhou M . The PHD finger: a versatile epigenome reader. Trends Biochem Sci. 2011; 36(7):364-72. PMC: 3130114. DOI: 10.1016/j.tibs.2011.03.005. View

20.

Lai B, Lee J, Jang Y, Wang L, Peng W, Ge K . MLL3/MLL4 are required for CBP/p300 binding on enhancers and super-enhancer formation in brown adipogenesis. Nucleic Acids Res. 2017; 45(11):6388-6403. PMC: 5499743. DOI: 10.1093/nar/gkx234. View