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Overview
Bromodomain adjacent to zinc finger 1A (BAZ1A) is a protein in humans encoded by the BAZ1A gene. The protein encoded by the BAZ1A gene contains the accessory subunit of the ATP-dependent chromatin assembly factor (ACF), which is a member of the imitation switch (ISWI) family of chromatin remodeling complexes including BAZ1B, BAZ2A and BAZ2B. BAZ1A structure contains a plant homeodomain (PHD) zinc finger at the N-terminus, a bromodomain at the C-terminus, a WAKZ motif and a LH (leucine-rich helical domain) motif [1]. BAZ1A is also known as ACF1, WALp1, hACF1 or WCRF180 [2].
BAZ1A function
BAZ1A encodes the chromatin-remodeling factor ACF1, which is a member of the ISWI chromatin remodeling complexes including the ATP-dependent chromatin assembly factor ACF, and the chromatin accessibility complex, CHRAC. BAZ1A (ACF1) has been implicated in a number of functions including chromatin remodeling, assembly and DNA repair. Together with the ISWI subunit, it has been shown to assemble regularly spaced nucleosome arrays in an ATP-dependent manner [3]. BAZ1A functions in certain DNA repair pathways including nucleotide excision repair (NER), non-homologous end-joining (NHEJ) and homologous recombination (HR), through interaction with a catalytic ATPase subunit, SMARCA5 [4]. BAZ1A has been shown to have a regulatory function in the transcriptional suppression of vitamin D3 receptor-regulated genes [5], and in the transcriptional regulation of stress-induced depressive-like behaviors [6]. A recent study with an identified variant in BAZ1A found that this affects the transcriptional regulatory function of ACF1, thus affecting the expression of genes crucial in vitamin D metabolism, the Wnt signalling pathway, and in proper synaptic function, highlighting the important role BAZ1A has in nervous system development and function [7].
Structural features, evolution and related structures
BAZ1A bromodomain histone-ligand recognition
BAZ1A bromodomain as well as BAZ1B a similar bromodomain family member, both have a conserved asparagine "anchor" residue which in functional bromodomains, hydrogen bonds with the carbonyl group of a bound acetyl-lysine ligand and it is crucial for the interaction. This suggests that BAZ1A and BAZ1B could potentially bind an acety-lysine ligand [8]. Also, BAZ1B has an hydrophobic valine "gatekeeper" residue which is found in the binding pockets of several acetyl-lysine binding bromodomains [9]. Surprisingly, the BAZ1A bromodomain gatekeeper was found to be a non-canonical glutamic acid residue which was found to be compatible with the bromodomain fold through the solving of the crystal structure of BAZ1A bromodomain. The glutamic acid residue introduces a negative charge on the side of the supposed binding pocket of BAZ1A which reduces its affinity for acetylated histone ligands [10].
BAZ1A-PHD binding to DNA
Ligand-interaction domain
Medical importance
References
- ↑ Jones MH, Hamana N, Nezu Ji, Shimane M. A novel family of bromodomain genes. Genomics. 2000 Jan 1;63(1):40-5. doi: 10.1006/geno.1999.6071. PMID:10662543 doi:http://dx.doi.org/10.1006/geno.1999.6071
- ↑ Racki LR, Yang JG, Naber N, Partensky PD, Acevedo A, Purcell TJ, Cooke R, Cheng Y, Narlikar GJ. The chromatin remodeller ACF acts as a dimeric motor to space nucleosomes. Nature. 2009 Dec 24;462(7276):1016-21. doi: 10.1038/nature08621. PMID:20033039 doi:http://dx.doi.org/10.1038/nature08621
- ↑ Ito T, Levenstein ME, Fyodorov DV, Kutach AK, Kobayashi R, Kadonaga JT. ACF consists of two subunits, Acf1 and ISWI, that function cooperatively in the ATP-dependent catalysis of chromatin assembly. Genes Dev. 1999 Jun 15;13(12):1529-39. PMID:10385622
- ↑ Aydin OZ, Vermeulen W, Lans H. ISWI chromatin remodeling complexes in the DNA damage response. Cell Cycle. 2014;13(19):3016-25. doi: 10.4161/15384101.2014.956551. PMID:25486562 doi:http://dx.doi.org/10.4161/15384101.2014.956551
- ↑ Ewing AK, Attner M, Chakravarti D. Novel regulatory role for human Acf1 in transcriptional repression of vitamin D3 receptor-regulated genes. Mol Endocrinol. 2007 Aug;21(8):1791-806. doi: 10.1210/me.2007-0095. Epub 2007 May, 22. PMID:17519354 doi:http://dx.doi.org/10.1210/me.2007-0095
- ↑ Sun H, Damez-Werno DM, Scobie KN, Shao NY, Dias C, Rabkin J, Koo JW, Korb E, Bagot RC, Ahn FH, Cahill ME, Labonte B, Mouzon E, Heller EA, Cates H, Golden SA, Gleason K, Russo SJ, Andrews S, Neve R, Kennedy PJ, Maze I, Dietz DM, Allis CD, Turecki G, Varga-Weisz P, Tamminga C, Shen L, Nestler EJ. ACF chromatin-remodeling complex mediates stress-induced depressive-like behavior. Nat Med. 2015 Oct;21(10):1146-53. doi: 10.1038/nm.3939. Epub 2015 Sep 21. PMID:26390241 doi:http://dx.doi.org/10.1038/nm.3939
- ↑ Zaghlool A, Halvardson J, Zhao JJ, Etemadikhah M, Kalushkova A, Konska K, Jernberg-Wiklund H, Thuresson AC, Feuk L. A Role for the Chromatin-Remodeling Factor BAZ1A in Neurodevelopment. Hum Mutat. 2016 Sep;37(9):964-75. doi: 10.1002/humu.23034. Epub 2016 Jul 8. PMID:27328812 doi:http://dx.doi.org/10.1002/humu.23034
- ↑ Flynn EM, Huang OW, Poy F, Oppikofer M, Bellon SF, Tang Y, Cochran AG. A Subset of Human Bromodomains Recognizes Butyryllysine and Crotonyllysine Histone Peptide Modifications. Structure. 2015 Sep 4. pii: S0969-2126(15)00329-9. doi:, 10.1016/j.str.2015.08.004. PMID:26365797 doi:http://dx.doi.org/10.1016/j.str.2015.08.004
- ↑ Filippakopoulos P, Picaud S, Mangos M, Keates T, Lambert JP, Barsyte-Lovejoy D, Felletar I, Volkmer R, Muller S, Pawson T, Gingras AC, Arrowsmith CH, Knapp S. Histone recognition and large-scale structural analysis of the human bromodomain family. Cell. 2012 Mar 30;149(1):214-31. PMID:22464331 doi:10.1016/j.cell.2012.02.013
- ↑ Oppikofer M, Sagolla M, Haley B, Zhang HM, Kummerfeld SK, Sudhamsu J, Flynn EM, Bai T, Zhang J, Ciferri C, Cochran AG. Non-canonical reader modules of BAZ1A promote recovery from DNA damage. Nat Commun. 2017 Oct 11;8(1):862. doi: 10.1038/s41467-017-00866-0. PMID:29021563 doi:http://dx.doi.org/10.1038/s41467-017-00866-0
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