히스톤

3. 분류

히스톤은 진핵생물의 세포와 진핵고균(Euryarchaea)이라 불리는 고균의 핵에서 발견되는 단백질이다. DNA와 결합하여 염색질을 형성하며, 크게 5가지 주요 클래스로 분류된다.^{[160][149][150]}

• H1/H5: 링커 히스톤이라고도 불리며, 뉴클레오솜 간의 DNA에 결합하여 염색질 응축을 돕는다.
• H2A
• H2B
• H3
• H4

위의 출력에서 `` 와 같은 내용들을 제거한다.

```최종 결과```

히스톤은 진핵생물의 세포와 진핵고균(Euryarchaea)이라 불리는 고균의 핵에서 발견되는 단백질이다. DNA와 결합하여 염색질을 형성하며, 크게 5가지 주요 클래스로 분류된다.^{[160][149][150]}

• H1/H5: 링커 히스톤이라고도 불리며, 뉴클레오솜 간의 DNA에 결합하여 염색질 응축을 돕는다.
• H2A
• H2B
• H3
• H4

3. 1. 히스톤 변이체

• H2A.Z: 활발하게 전사되는 유전자의 촉진부위(promoter)에 결합하며, 이형염색질 형성에도 관여한다.
• H2A.X: DNA 이중 가닥이 손상된 부위에 결합하여 DNA 수리가 진행 중임을 표시한다.
• CENP-A: 염색체의 동원체 부위에만 결합하는 히스톤으로, 동원체 형성에 관여한다.

4. 구조

H2A, H2B, H3, H4는 각각 2개씩 모여 8량체인 핵심 히스톤을 구성한다.^[151] 이들은 뉴클레오솜 핵 부분에 존재하며 146 염기쌍의 DNA를 감는다. DNA는 하나의 히스톤을 왼손 방향으로 1.65회 정도 감는다.^[151] 연결 히스톤 H1은 뉴클레오솜 DNA의 감기지 않은 부분에 결합하여 DNA를 고정하고 더 높은 차원의 구조를 형성한다.^[152]

• DNA 인산 골격(전체적으로 음전하)과 중심 히스톤(전체적으로 양전하) 사이에서 H2B, H3, H4의 알파 나선에 의한 나선 쌍극자
• DNA 골격과 히스톤 중심 사슬의 아민 그룹 사이의 수소 결합
• 히스톤과 DNA의 디옥시리보스 사이의 비극성 상호작용
• 염기성 아미노산(특히 라이신과 아르기닌)의 측쇄와 DNA 인산기의 산소 사이의 염 연결과 수소 결합
• H3와 H2B의 N-말단 꼬리가 DNA 분자의 작은 홈으로 파고들면서 생기는 비특이성 삽입

5. 기능

히스톤은 긴 DNA 분자를 접어 핵 내에 수납하고, DNA 복제, 전사, 수선 등 다양한 생물학적 과정에 관여하는 단백질이다. 히스톤과 DNA의 무게비는 거의 1:1이다.

히스톤은 크게 6종류로 나뉜다.^{[160][149][150]}

• H1 (연결 히스톤, H5와도 관련 있음.)
• H2

• H3
• H4
• 고균 히스톤

5. 1. DNA 응축

5. 2. 염색질 조절

5. 2. 1. 히스톤 변형의 종류

• 히스톤의 이름 (예: H3)
• 단일 문자 아미노산 약어 (예: 라이신의 K)와 단백질 내 아미노산 위치
• 변형의 유형 (Me: 메틸, P: 인산, Ac: 아세틸, Ub: 유비퀴틴)
• 변형의 수 (메틸화의 경우에만 잔기당 2개 이상 발생할 수 있는 것으로 알려져 있다. 1, 2 또는 3은 모노-, 디-, 또는 트리메틸화이다)

5. 2. 2. 히스톤 코드 가설

5. 3. 히스톤 샤페론

이 외에도 아프리카발톱개구리의 난모세포에서 발견된 뉴클레오플라스민(nucleoplasmin)이 있다. 1977년 뉴클레오플라스민의 발견으로 히스톤 샤페론 개념이 처음 제안되었다.^[138]

6. 진화

히스톤은 진핵생물과 고세균의 핵에서 발견되지만, 세균에서는 발견되지 않는다.^[26] 와편모조류라는 단세포 조류는 한때 히스톤이 없는 유일한 진핵생물로 여겨졌으나,^[21] 이후 연구에서 DNA에 히스톤 유전자가 있다는 것이 밝혀졌다.^[22] 고세균의 히스톤은 진핵생물 히스톤의 진화적 전구체와 매우 유사할 수 있다.^[26]

히스톤 단백질은 진핵생물에서 매우 잘 보존되어 있는데, 이는 핵의 생물학에서 히스톤의 중요한 역할을 보여준다.^[2] 중심 히스톤은 다양한 종 사이에서 아미노산 서열 변화가 매우 적다. 연결 히스톤은 종종 한 종에서 하나 이상의 형태를 가지며, 중심 히스톤보다 덜 보존되어 있다.

주요 히스톤에는 몇 가지 변이체 형태가 존재한다. 이들은 아미노산 서열과 핵심 구조는 유사하지만, 고유한 특징을 가진 "소량 히스톤"이다. 소량 히스톤은 염색질 대사에서 특정 기능을 수행한다. 예를 들어, 히스톤 H3과 유사한 CENPA는 염색체의 동원체에만 결합한다. H2A 변이체인 H2A.Z는 활발하게 전사되는 유전자의 프로모터와 관련이 있으며, 이질염색질의 확산을 막는 데 관여한다.^[28] H2A.Z는 게놈 안정성에도 역할을 한다.^[29] 또 다른 H2A 변이체인 H2A.X는 DNA 이중 가닥 절단 부위에 결합하여 DNA 복구가 진행 중임을 표시한다.^[30] 히스톤 H3.3은 활발하게 전사되는 유전자의 몸체와 관련이 있다.^[31]

고세균이 히스톤과 유사한 단백질을 가지고 있다는 사실로부터, '''히스톤 유사 단백질'''은 진핵생물과 고세균이 분리되기 전부터 존재했을 것으로 추정된다.^[143][144]

참조

_[1] 서적 Collins Dictionary of Human Biology HarperCollins
_[2] 서적 Lehninger Principles of Biochemistry https://archive.org/[...] W.H. Freeman
_[3] 논문 Histone H2A variants H2AX and H2AZ https://www.scienced[...] 2002-04
_[4] 웹사이트 Histone Variants Database 2.0 https://www.ncbi.nlm[...] National Center for Biotechnology Information 2017-01-13
_[5] 논문 Recognition and classification of histones using support vector machine http://eprints.ucm.e[...] 2019-03-23
_[6] 서적 Basic Genetics https://archive.org/[...] Jones and Bartlett Publishers
_[7] 논문 Histone structure and nucleosome stability 2005-10
_[8] 논문 Crystal structure of the nucleosome core particle at 2.8 A resolution https://www.nature.c[...] 1997-09
_[9] 서적 DNA simplified: the hitchhiker's guide to DNA AACC Press
_[10] 논문 A standardized nomenclature for mammalian histone genes 2022-10
_[11] 논문 Histone H3.3 maintains genome integrity during mammalian development 2015-07
_[12] 논문 HistoneDB 2.0: a histone database with variants--an integrated resource to explore histones and their variants 2016
_[13] 논문 MS_HistoneDB, a manually curated resource for proteomic analysis of human and mouse histones 2017
_[14] 논문 Evidence for a human histone gene cluster containing H2B and H2A pseudogenes 1984-04
_[15] 논문 Association of a human H1 histone gene with an H2A pseudogene and genes encoding H2B.1 and H3.1 histones 1993-08
_[16] 논문 Structure of histone-based chromatin in Archaea 2017-08
_[17] 논문 Long distance PELDOR measurements on the histone core particle 2009-02
_[18] 논문 The tale beyond the tail: histone core domain modifications and the regulation of chromatin structure 2006-05-19
_[19] 논문 Scratching the (lateral) surface of chromatin regulation by histone modifications https://www.nature.c[...] 2013-06
_[20] 서적 Fundamental Molecular Biology John Wiley & Sons
_[21] 논문 Those amazing dinoflagellate chromosomes 2003-08
_[22] 논문 Chromatin: packaging without nucleosomes 2012-12
_[23] 논문 Origin of H1 linker histones 2001-01
_[24] 논문 On the origin of the histone fold 2007-03
_[25] 논문 The origin of chromosomal histones in a 30S ribosomal protein https://www.scienced[...] 2020-02
_[26] 논문 Structure and function of archaeal histones 2018-09
_[27] 논문 Nuclear and chromatin composition of mammalian gametes and early embryos https://cdnsciencepu[...]
_[28] 논문 Variant histone H2A.Z is globally localized to the promoters of inactive yeast genes and regulates nucleosome positioning 2005-12
_[29] 논문 Precise deposition of histone H2A.Z in chromatin for genome expression and maintenance https://www.scienced[...] 2011-10
_[30] 논문 A critical role for histone H2AX in recruitment of repair factors to nuclear foci after DNA damage
_[31] 논문 The histone variant H3.3 marks active chromatin by replication-independent nucleosome assembly 2002-06
_[32] 논문 The language of covalent histone modifications https://ui.adsabs.ha[...] 2000-01
_[33] 논문 Translating the histone code http://www.gs.washin[...] 2001-08
_[34] 논문 Immunohistochemical Analysis of Histone H3 Modifications in Germ Cells during Mouse Spermatogenesis 2011-08
_[35] 논문 Histone H3K4 demethylases are essential in development and differentiation https://cdnsciencepu[...] 2007-08
_[36] 논문 High-resolution profiling of histone methylations in the human genome 2007-05
_[37] 논문 DOT1L/KMT4 recruitment and H3K79 methylation are ubiquitously coupled with gene transcription in mammalian cells 2008-04
_[38] 논문 Determination of enriched histone modifications in non-genic portions of the human genome 2009-03
_[39] 논문 The landscape of histone modifications across 1% of the human genome in five human cell lines 2007-06
_[40] 논문 H4K20me3 co-localizes with activating histone modifications at transcriptionally dynamic regions in embryonic stem cells 2018-07
_[41] 논문 H3 lysine 4 is acetylated at active gene promoters and is regulated by H3 lysine 4 methylation 2011-03
_[42] 논문 Histone H3K27ac separates active from poised enhancers and predicts developmental state 2010-12
_[43] 논문 Histone serotonylation is a permissive modification that enhances TFIID binding to H3K4me3 2019-03
_[44] 논문 Citrullination regulates pluripotency and histone H1 binding to chromatin https://www.reposito[...] 2014-03
_[45] 논문 Histone deimination antagonizes arginine methylation 2004-09
_[46] 논문 The Paf1 complex is required for histone H3 methylation by COMPASS and Dot1p: linking transcriptional elongation to histone methylation 2003-03
_[47] 논문 Targeted recruitment of Set1 histone methylase by elongating Pol II provides a localized mark and memory of recent transcriptional activity 2003-03
_[48] 논문 Genomic maps and comparative analysis of histone modifications in human and mouse 2005-01
_[49] 논문 COMPASS, a histone H3 (Lysine 4) methyltransferase required for telomeric silencing of gene expression 2002-03
_[50] 논문 The Saccharomyces cerevisiae Set1 complex includes an Ash2 homologue and methylates histone 3 lysine 4 2001-12
_[51] 논문 A trithorax-group complex purified from Saccharomyces cerevisiae is required for methylation of histone H3 2002-01
_[52] 논문 The Bur1/Bur2 complex is required for histone H2B monoubiquitination by Rad6/Bre1 and histone methylation by COMPASS 2005-11
_[53] 논문 Regulation of the ubiquitin-conjugating enzyme hHR6A by CDK-mediated phosphorylation 2002-04
_[54] 논문 Rad6-dependent ubiquitination of histone H2B in yeast https://www.science.[...] 2000-01
_[55] 논문 Ubiquitination of histone H2B regulates H3 methylation and gene silencing in yeast https://www.nature.c[...] 2002-07
_[56] 논문 Methylation of histone H3 by COMPASS requires ubiquitination of histone H2B by Rad6 2002-08
_[57] 논문 Set2 is a nucleosomal histone H3-selective methyltransferase that mediates transcriptional repression 2002-03
_[58] 논문 Association of the histone methyltransferase Set2 with RNA polymerase II plays a role in transcription elongation 2002-12
_[59] 논문 Histone H3 methylation by Set2 directs deacetylation of coding regions by Rpd3S to suppress spurious intragenic transcription 2005-11
_[60] 논문 Cotranscriptional set2 methylation of histone H3 lysine 36 recruits a repressive Rpd3 complex 2005-11
_[61] 논문 Eaf3 chromodomain interaction with methylated H3-K36 links histone deacetylation to Pol II elongation 2005-12
_[62] 논문 Histone methyltransferase activity associated with a human multiprotein complex containing the Enhancer of Zeste protein 2002-11
_[63] 논문 Role of histone H3 lysine 27 methylation in Polycomb-group silencing https://www.science.[...] 2002-11
_[64] 논문 Polycomb group proteins Ring1A/B link ubiquitylation of histone H2A to heritable gene silencing and X inactivation 2004-11
_[65] 논문 Role of histone H2A ubiquitination in Polycomb silencing 2004-10
_[66] 논문 RYBP-PRC1 complexes mediate H2A ubiquitylation at polycomb target sites independently of PRC2 and H3K27me3 2012-02
_[67] 논문 PCGF homologs, CBX proteins, and RYBP define functionally distinct PRC1 family complexes 2012-02
_[68] 논문 RNAi-mediated targeting of heterochromatin by the RITS complex 2004-01
_[69] 논문 Regulation of chromatin structure by site-specific histone H3 methyltransferases https://www.nature.c[...] 2000-08
_[70] 논문 Selective recognition of methylated lysine 9 on histone H3 by the HP1 chromo domain https://www.nature.c[...] 2001-03
_[71] 논문 Methylation of histone H3 lysine 9 creates a binding site for HP1 proteins https://www.nature.c[...] 2001-03
_[72] 논문 Binding of DNA-bending non-histone proteins destabilizes regular 30-nm chromatin structure 2017-01
_[73] 논문 A silencing pathway to induce H3-K9 and H4-K20 trimethylation at constitutive heterochromatin 2004-06
_[74] 논문 Heterochromatin and tri-methylated lysine 20 of histone H4 in animals 2004-05
_[75] 논문 A bivalent chromatin structure marks key developmental genes in embryonic stem cells 2006-04
_[76] 논문 DNA double-stranded breaks induce histone H2AX phosphorylation on serine 139 1998-03
_[77] 논문 Genomic instability in mice lacking histone H2AX 2002-05
_[78] 논문 Distribution and dynamics of chromatin modification induced by a defined DNA double-strand break 2004-10
_[79] 논문 Megabase chromatin domains involved in DNA double-strand breaks in vivo 1999-09
_[80] 논문 MDC1 is a mediator of the mammalian DNA damage checkpoint https://www.nature.c[...] 2003-02
_[81] 논문 Assembly and function of DNA double-strand break repair foci in mammalian cells https://www.scienced[...] 2010-12
_[82] 논문 Characterization of lysine 56 of histone H3 as an acetylation site in Saccharomyces cerevisiae 2005-07
_[83] 논문 A role for cell-cycle-regulated histone H3 lysine 56 acetylation in the DNA damage response https://www.nature.c[...] 2005-07
_[84] 논문 Yeast Rtt109 promotes genome stability by acetylating histone H3 on lysine 56 2007-02
_[85] 논문 Rtt109 acetylates histone H3 lysine 56 and functions in DNA replication https://www.science.[...] 2007-02
_[86] 논문 CBP/p300-mediated acetylation of histone H3 on lysine 56 2009-05
_[87] 논문 Acetylation of lysine 56 of histone H3 catalyzed by RTT109 and regulated by ASF1 is required for replisome integrity 2007-09
_[88] 논문 Histone H3 lysine 56 acetylation and the response to DNA replication fork damage 2012-01
_[89] 논문 Modulation of histone H3 lysine 56 acetylation as an antifungal therapeutic strategy 2010-07
_[90] 논문 The histone mark H3K36me3 regulates human DNA mismatch repair through its interaction with MutSα 2013-04
_[91] 논문 Clustered Mutation Signatures Reveal that Error-Prone DNA Repair Targets Mutations to Active Genes 2017-07
_[92] 논문 A cascade of histone modifications induces chromatin condensation in mitosis https://www.science.[...] 2014-01
_[93] 논문 Regulation of chromatin structure by histone H3S10 phosphorylation https://link.springe[...] 2006
_[94] 논문 R loops are linked to histone H3 S10 phosphorylation and chromatin condensation 2013-11
_[95] 논문 Apoptotic phosphorylation of histone H2B is mediated by mammalian sterile twenty kinase 2003-05
_[96] 논문 Sterile 20 kinase phosphorylates histone H2B at serine 10 during hydrogen peroxide-induced apoptosis in S. cerevisiae 2005-01
_[97] 논문 Transcriptional and epigenetic mechanisms of addiction 2011-10
_[98] 논문 Histone-mediated epigenetics in addiction Academic Press 2014
_[99] 논문 Epigenetic regulation in substance use disorders 2010-04
_[100] 웹사이트 Is nicotine addictive? https://www.drugabus[...]
_[101] 논문 Molecular mechanism for a gateway drug: epigenetic changes initiated by nicotine prime gene expression by cocaine 2011-11
_[102] 논문 Molecular neurobiology of addiction: what's all the (Δ)FosB about? https://www.tandfonl[...] 2014-11
_[103] 논문 DeltaFosB: a sustained molecular switch for addiction 2001-09
_[104] 논문 Ethanol induces epigenetic modulation of prodynorphin and pronociceptin gene expression in the rat amygdala complex https://link.springe[...] 2013-02
_[105] 웹사이트 What is the scope of methamphetamine abuse in the United States? https://www.drugabus[...]
_[106] 논문 Epigenetic landscape of amphetamine and methamphetamine addiction in rodents 2015
_[107] 논문 Using c-fos to study neuronal ensembles in corticostriatal circuitry of addiction 2015-12
_[108] 논문 Cln3 activates G1-specific transcription via phosphorylation of the SBF bound repressor Whi5 2004-06
_[109] 논문 Identification of a new set of cell cycle-regulatory genes that regulate S-phase transcription of histone genes in Saccharomyces cerevisiae 1992-11
_[110] 논문 A role for transcriptional repressors in targeting the yeast Swi/Snf complex 1999-07
_[111] 논문 A novel zinc finger protein is associated with U7 snRNP and interacts with the stem-loop binding protein in the histone pre-mRNP to stimulate 3'-end processing 2002-01
_[112] 논문 A 3' exonuclease that specifically interacts with the 3' end of histone mRNA 2003-08
_[113] 논문 Phosphorylation of stem-loop binding protein (SLBP) on two threonines triggers degradation of SLBP, the sole cell cycle-regulated factor required for regulation of histone mRNA processing, at the end of S phase 2003-03
_[114] 논문 Cajal bodies are linked to genome conformation 2016-03
_[115] 논문 NPAT links cyclin E-Cdk2 to the regulation of replication-dependent histone gene transcription 2000-09
_[116] 서적 The Nucleohistones Holden-Day, Inc 1965
_[117] 논문 Chapters from my life 1994
_[118] 논문 Histone, a suppressor of chromosomal RNA synthesis 1962-07
_[119] 논문 Huang R C & Bonner J. Histone, a suppressor of chromosomal RNA synthesis. Proc. Nat. Acad. Sci. US 48:1216-22, 1962. http://garfield.libr[...] 1978-03-20
_[120] 서적 The Nucleohistones Holden-Day Inc 1965
_[121] 논문 Calf and pea histone IV. 3. Complete amino acid sequence of pea seedling histone IV; comparison with the homologous calf thymus histone 1969-10
_[122] 논문 Acetylation and methylation of histones and their possible role in the regulation of RNA synthesis 1964-05
_[123] 논문 Nucleosomes inhibit the initiation of transcription but allow chain elongation with the displacement of histones https://pubmed.ncbi.[...] 1987-04
_[124] 논문 Extremely conserved histone H4 N terminus is dispensable for growth but essential for repressing the silent mating loci in yeast https://www.cell.com[...] 1988-10
_[125] 논문 RNA synthesis and histone acetylation during the course of gene activation in lymphocytes 1966-04
_[126] 논문 Yeast histone H4 N-terminal sequence is required for promoter activation in vivo https://www.cell.com[...] 1991-06
_[127] 논문 Tetrahymena histone acetyltransferase A: a homolog to yeast Gcn5p linking histone acetylation to gene activation 1996-03
_[128] 논문 The conformation of histone H5. Isolation and characterisation of the globular segment 1978-08
_[129] 논문 The language of covalent histone modifications
_[130] 논문 The enhancement of histone H4 and H2A serine 1 phosphorylation during mitosis and S-phase is evolutionarily conserved
_[131] 논문 Surfing chromosomes (and Survivin)
_[132] 논문 The enhancement of histone H4 and H2A serine 1 phosphorylation during mitosis and S-phase is evolutionarily conserved
_[133] 논문 NAD+-dependent deacetylation of H4 lysine 16 by class III HDACs
_[134] 논문 Histone H4 lysine 20 methylation: key player in epigenetic regulation of genomic integrity
_[135] 논문 Histone chaperones in nucleosome assembly and human disease
_[136] 논문 The histone chaperone FACT: structural insights and mechanisms for nucleosome reorganization
_[137] 논문 Nap1: taking a closer look at a juggler protein of extraordinary skills
_[138] 논문 Nucleosomes are assembled by an acidic protein which binds histones and transfers them to DNA
_[139] 논문 SWI/SNF chromatin-remodeling factors: multiscale analyses and diverse functions
_[140] 논문 Chromatin remodelling in mammalian cells by ISWI-type complexes--where, when and why?
_[141] 논문 The Mi-2/NuRD complex: a critical epigenetic regulator of hematopoietic development, differentiation and cancer
_[142] 논문 Chromatin remodelling beyond transcription: the INO80 and SWR1 complexes
_[143] 논문 Archaeal histones and the origin of the histone fold
_[144] 논문 Chromatin structure and dynamics in hot environments: architectural proteins and DNA topoisomerases of thermophilic archaea
_[145] 논문 Archaeal nucleosomes
_[146] 논문 Structure of histone-based chromatin in Archaea
_[147] 논문 Chromatin is an ancient innovation conserved between Archaea and Eukarya
_[148] 논문 Old cogs, new tricks: the evolution of gene expression in a chromatin context
_[149] 논문 Recognition and classification of histones using support vector machine
_[150] 서적 Basic Genetics https://archive.org/[...] Jones and Bartlett Publishers
_[151] 문서 Luger, et al, Nature 389: 251, 1997 http://www.pdb.org/p[...] PDB entry 1AOI
_[152] 서적 DNA simplified: the hitchhiker's guide to DNA https://archive.org/[...] AACC Press
_[153] 논문 Role of Histone Acetylation in the Assembly and Modulation of Chromatin Structures 2018-05-23
_[154] 논문 The language of covalent histone modifications 2000-01
_[155] 논문 Translating the histone code 2001-08
_[156] 논문 The conformation of the histone H3 tail inhibits association of the BPTF PHD finger with the nucleosome 2018-04-12
_[157] 논문 Epigenetic regulation in psychiatric disorders 2007-05
_[158] 논문 ΔFosB Mediates Epigenetic Desensitization of the c-fos Gene After Chronic Amphetamine Exposure 2008-07-16
_[159] 논문 Histone-like protein H1 (H-NS), DNA supercoiling, and gene expression in bacteria 1990-11
_[160] 서적 Lehninger Principles of Biochemistry W.H. Freeman
_[161] 논문 The histone variant H3.3 marks active chromatin by replication-independent nucleosome assembly 2002-06