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Primate-Specific Histone Variants

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Primate-Specific Histone Variants Genome Primate-specific histone variants Journal: Genome Manuscript ID gen-2020-0094.R1 Manuscript Type: Mini Review Date Submitted by the 16-Sep-2020 Author: Complete List of Authors: Ding, Dongbo; Hong Kong University of Science and Technology School of Science, Division of Life Science NGUYEN, Thi Thuy; Hong Kong University of Science and Technology School of Science, Division of Life Science Pang, Matthew Yu Hin; Hong Kong University of Science and Technology School of Science, Division of Life Science Ishibashi, DraftToyotaka; Hong Kong University of Science and Technology School of Science, Division of Life Science Keyword: histone variant, H2BFWT, H3.5, H3.X, H3.Y Is the invited manuscript for consideration in a Special Genome Biology Issue? : © The Author(s) or their Institution(s) Page 1 of 28 Genome 1 Primate-specific histone variants 2 Dongbo Ding1, Thi Thuy Nguyen1, Matthew Y.H. Pang1 and Toyotaka 3 Ishibashi1 4 1. Division of Life Science, The Hong Kong University of Science and Technology, 5 Clear Water Bay, NT, HKSAR, China 6 7 8 9 10 11 12 Draft 13 14 15 16 17 18 19 Correspondence should be addressed to : 20 Toyotaka Ishibashi 21 The Hong Kong University of Science and Technology 22 Clear Water Bay, NT, HKSAR, China 23 E-mail: [email protected] 24 Phone: +852-3469-2238 25 Fax: +852-2358-1552 26 © The Author(s) or their Institution(s) Genome Page 2 of 28 27 Abstract 28 29 Canonical histones (H2A, H2B, H3, and H4) are present in all eukaryotes where they 30 package genomic DNA and participate in numerous cellular processes, such as 31 transcription regulation and DNA repair. In addition to the canonical histones, there 32 are many histone variants, which have different amino acid sequences, possess tissue- 33 specific expression profiles, and function distinctly from the canonical counterparts. A 34 number of histone variants, including both core histones (H2A/H2B/H3/H4) and 35 linker histones (H1/H5), have been identified to date. Htz1 (H2A.Z) and CENP-A 36 (CenH3) are present from yeasts to mammals, and H3.3 is present from Tetrahymena 37 to humans. In addition to the prevalent variants, others like H3.4 (H3t), H2A.Bbd, and 38 TH2B, as well as several H1 variants,Draft are found to be specific to mammals. Among 39 them, H2BFWT, H3.5, H3.X, H3.Y, and H4G are unique to primates (or Hominidae). 40 In this review, we focus on localization and function of primate- or hominidae- 41 specific histone variants. 42 43 44 45 Key Words 46 47 Histone variants, H2BFWT, H3.5, H3.X, H3.Y, H4G 48 © The Author(s) or their Institution(s) Page 3 of 28 Genome 49 50 1. Telomere-localized and spermatogenesis-specific histone variants, H2BFWT 51 52 Histone H2B, one of the four canonical histones involved in chromatin formation, 53 has several canonical isoforms (Molden et al. 2015) and two variants: TH2B and 54 H2BFWT, both of which have been identified as testis-specific histones. TH2B is 55 present in later stages of spermatogenesis and is expressed in most mammalian 56 species (Montellier et al. 2013), whereas H2BFWT is expressed only in primates. 57 H2BFWT is also known as H2BW1, is located at the locus Xq22.2 in humans (Table 58 1). The H2BFWT protein shares 43% amino acid sequence identity with the 59 canonical H2B, and 46% identity with TH2B (Figure 1). H2BFWT was reported to 60 be 153 amino acid residues long inDraft vivo with an extended N-terminal tail compared 61 to canonical H2B (Boulard et al. 2006). 62 63 GFP-H2BFWT was found to mainly localize in the telomeric region in Chinese 64 hamster immortal lung fibroblasts (the V79 cell line) (Churikov et al. 2004). 65 However, there is limited knowledge about its function in the telomeric region. 66 H2BFWT can also be loaded into nucleosomes using in vitro salt gradient dialysis 67 methods, and these reconstituted H2BFWT nucleosomes can be remodeled and 68 mobilized by the SWI/SNF chromatin remodeling complex more efficiently than that 69 the canonical nucleosomes (Boulard et al. 2006). In contrast to canonical H2B, 70 H2BFWT was reported to be unable to recruit chromosome condensation factors and 71 participate in the assembly of mitotic chromosomes (Boulard et al. 2006). 72 © The Author(s) or their Institution(s) Genome Page 4 of 28 73 Several studies have suggested a relationship between single nucleotide 74 polymorphisms (SNPs) in H2BFWT and defects in male fertility (Lee et al. 2009; 75 Rafatmanesh et al. 2018; Ying et al. 2012). In particular, three groups have linked the 76 -9C > T mutation (rs7885967) within the 5’ untranslated region of H2BFWT to non- 77 azoospermia (p = 0.018), a reduced sperm count (p = 0.0127) and a weakened sperm 78 vitality (p = 0.0076) (Lee et al. 2009; Rafatmanesh et al. 2018; Ying et al. 2012). A 79 related investigation by Ying et al. revealed that the 368A > G mutation (rs553509) 80 increased the risk of male sterility (Ying et al. 2012)(Figure 2). 81 82 A more contemporary analysis assessing copy number variations in chromosome X 83 revealed that 5 out of 42 female participants with premature ovarian failure suffer 84 from either gains or losses of genomicDraft regions containing H2BFWT and H2BFM (an 85 uncharacterized histone variant located near H2BFWT) (Quilter et al. 2010). 86 Considering the highly testis-specific expression pattern of H2BFWT and the 87 detectable expression of H2BFM in the ovary (Papatheodorou et al. 2020), it is not 88 unreasonable to speculate that the premature ovarian failure phenotype stems from 89 the deletion of H2BFM but not H2BFWT. However, the possibilities of a correlation 90 between mutations in both H2BFWT and H2BFM, and premature ovarian failures 91 cannot be ignored, especially when detailed expression profiles of H2BFWT and 92 H2BFM in female reproductive organs are currently unavailable. Compounded by 93 the fact that the biological role of H2BFM has yet to be explored, further research is 94 necessary to evaluate these hypotheses. Although H2BFWT SNPs increase the 95 probability of infertility, it is possible that H2BFWT is not the only causative factor. 96 It would also be interesting to study its combination with another histone variant’s 97 mutation contributing to infertility. Further characterization of H2BFWT would be © The Author(s) or their Institution(s) Page 5 of 28 Genome 98 helpful to understand how it might contribute to spermatogenesis and other cellular 99 processes. 100 101 Regarding the H2B family, other than H2BFWT, little attention has been given to 102 multi-copied canonical H2B isoforms, which differ from each other by a few amino 103 acids. Most of them are currently grouped together as canonical H2Bs due to their 104 high similarity (Molden et al. 2015). Most changes in these isoforms are small and 105 have minor effects on the H2B protein structure, although some isoforms such as 106 H2B1L, H2B1M, and H2B1A could possess an alternative N-terminal tail 107 conformation (Molden et al. 2015). It remains unknown if these structural 108 modifications can cause distinct functions or localizations compared to canonical 109 H2B, but it would be interestingDraft to study how the N-terminal tail of H2B can 110 contribute to nucleosome stability, change the chromatin structure, interact with other 111 proteins, cause distinct genomic localization, and potentially alter post-translational 112 modification patterns if critical amino acid residues are changed. 113 114 2. Testis-specific histone variant H3.5 regulates spermatogenesis while H3.X and 115 H3.Y express in the brain 116 117 The histone H3 family has several histone variants, but although their sequences are 118 similar, they have distinct functions (Buschbeck and Hake 2017). For example, H3.3 119 is widely expressed and is localized in the promoter region of actively expressed 120 genes, while another histone variant, H3T (H3.4), is only present in the testis and 121 plays a critical role in the dynamics of chromatin transitions during spermatogenesis 122 (Ausio et al. 2016; Yuen et al. 2014). In primates, three additional H3 variants have © The Author(s) or their Institution(s) Genome Page 6 of 28 123 been identified; H3.5 (also known as H3.3C) (Schenk et al. 2011; Ederveen et al. 124 2011), H3.X, and H3.Y (Wiedemann et al. 2010). 125 126 The H3.5 gene is localized in the 12p11.21 region of human chromosome 12 (Schenk 127 et al. 2011). The amino acid sequence of H3.5 is most similar to that of histone 128 variant H3.3, which is involved in the maintenance of transcriptionally active 129 chromatin (Mito et al. 2005). The H3.X and H3.Y genes were identified at the same 130 time and are located at the 5p15.1 chromosome region in humans (Wiedemann et al. 131 2010). Both H3.X and H3.Y are expressed in the same tissues and are considered to 132 have similar functions, including regulating the cell cycle and facilitating DUX4 133 target genes expression (Resnick etDraft al. 2019; Wiedemann et al. 2010). 134 135 Histone variant H3.5 varies by five amino acid residues from H3.3 (Figure 1). As a 136 result, the H3.5 nucleosome has lower nucleosome stability than the H3.3 137 nucleosome, but it is more stable than the H3.4 (H3T) nucleosome (Urahama et al. 138 2016). This decrease in nucleosome stability can mainly be attributed to the H3.5L103 139 residue which weakens the interaction between H3.5 and H4 (Urahama et al. 2016). 140 The H3.5/H4 tetrasome is also less stable than the H3.3/H4 tetrasome (Urahama et al.
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