Chromatin Structure and Domains


In eukaryotes, the deoxyribonucleic acid (DNA) molecule is associated with nuclear proteins called histones to form chromatin. This structure is not only essential to compact DNA to fit into the cell nucleus but also contributes to the regulation of DNA‐ dependent molecular mechanisms. Epigenetic modifications such as post‐translational modifications of histones and also precise spatial organisation of chromosomes are now recognised as important features for chromatin dynamics, allowing proper transcription regulation, a major issue of cell differentiation during the development of multicellular organisms.

Key Concepts

  • Chromatin is a highly structured entity with an important flexibility.
  • The large repertoire of epigenetic modifications offers a wide range of specific molecular and cellular responses.
  • Together with genetic information, epigenetic marks play a critical role in the transmission of gene regulation.
  • Nuclear organisation of chromosomes participates in the inheritance of chromatin states.
  • Chromosomes organise into functional domains important for DNA regulation.

Keywords: histones; nucleosomes; chromatin; chromosomes; nuclear organisation

Figure 1. Schematic representation of different post‐translational modifications identified on histones. Methylation is marked in red, acetylation in blue, phosphorylation in green and ubiquitination in purple. Position of each amino acid modified is indicated below.
Figure 2. Different chromosome organisations. (a) Chromosomes do not globally intermingle in the nucleus during interphase, (b) Rabl configuration of chromosomes. Centromeres of each chromosome are connected at the apical pole of the nucleus and formed the chromocenter, whereas telomeres are preferentially found in the basal pole of the nucleus, (c) radial (left) and relative (right) positioning of human chromosomes. In the radial positioning, distances are measured according to the centre of the nucleus (arrows), and in the relative positioning, distances are measured between chromosomes (arrows).
Figure 3. Nuclear positioning of genes: (a) looping out of specific locus upon activation, (b) concentration of rDNA loci located on different chromosomes to form nucleolus, (c) natural intermingling between different chromosome territories and (d) long‐distance chromosomal interactions between two loci into repressive bodies (blue, e.g. Polycomb bodies), or into active RNA factories (red).
Figure 4. Functional organisation of chromatin in the nucleus. (a) Chromosome territory is composed of active (pink) and inactive (purple) compartment. (b) Each chromatin compartment is organised in sub‐regions of important genomic interactions. These regions also called topological associated domains (TADs) are necessary for partitioning genomic DNA of each chromosome.


Albiez H, Cremer M, Tiberi C, et al. (2006) Chromatin domains and the interchromatin compartment form structurally defined and functionally interacting nuclear networks. Chromosome Research 14 (7): 707–733.

Bannister AJ and Kouzarides T (2011) Regulation of chromatin by histone modifications. Cell Research 21 (3): 381–395.

Barski A, Cuddapah S, Cui K, et al. (2007) High‐resolution profiling of histone methylations in the human genome. Cell 129 (4): 823–837.

Belton JM, McCord RP, Gibcus JH, et al. (2012) Hi‐C: a comprehensive technique to capture the conformation of genomes. Methods 58 (3): 268–276.

Bernstein BE, Mikkelsen TS, Xie X, et al. (2006) A bivalent chromatin structure marks key developmental genes in embryonic stem cells. Cell 125 (2): 315–326.

Boyle S, Gilchrist S, Bridger JM, et al. (2001) The spatial organization of human chromosomes within the nuclei of normal and emerin‐mutant cells. Human Molecular Genetics 10 (3): 211–219.

Brownell JE, Zhou J, Ranalli T, et al. (1996) Tetrahymena histone acetyltransferase A: a homolog to yeast Gcn5p linking histone acetylation to gene activation. Cell 84 (6): 843–851.

Cao R, Wang L, Wang H, et al. (2002) Role of histone H3 lysine 27 methylation in Polycomb‐group silencing. Science 298 (5595): 1039–1043.

Cavalli G and Misteli T (2013) Functional implications of genome topology. Nature Structural and Molecular Biology 20 (3): 290–299.

Chambeyron S and Bickmore WA (2004) Chromatin decondensation and nuclear reorganization of the HoxB locus upon induction of transcription. Genes and Development 18 (10): 1119–1130.

Cremer T, Cremer C, Schneider T, et al. (1982) Analysis of chromosome positions in the interphase nucleus of Chinese hamster cells by laser‐UV‐microirradiation experiments. Human Genetics 62 (3): 201–209.

Croft JA, Bridger JM, Boyle S, et al. (1999) Differences in the localization and morphology of chromosomes in the human nucleus. Journal of Cell Biology 145 (6): 1119–1131.

De Napoles M, Mermoud JE, Wakao R, et al. (2004) Polycomb group proteins Ring1A/B link ubiquitylation of histone H2A to heritable gene silencing and X inactivation. Developmental Cell 7 (5): 663–676.

Dixon JR, Selvaraj S, Yue F, et al. (2012) Topological domains in mammalian genomes identified by analysis of chromatin interactions. Nature 485 (7398): 376–380.

Duncan IW (2002) Transvection effects in Drosophila. Annual Review of Genetics 36: 521–556.

Ferrai C, Xie SQ, Luraghi P, et al. (2010) Poised transcription factories prime silent uPA gene prior to activation. PLoS Biology 8 (1): e1000270.

Filion GJ, van Bemmel JG, Braunschweig U, et al. (2010) Systematic protein location mapping reveals five principal chromatin types in Drosophila cells. Cell 143 (2): 212–224.

Ginjala V, Nacerddine K, Kulkarni A, et al. (2011) BMI1 is recruited to DNA breaks and contributes to DNA damage‐induced H2A ubiquitination and repair. Molecular and Cellular Biology 31 (10): 1972–1982.

Guelen L, Pagie L, Brasset E, et al. (2008) Domain organization of human chromosomes revealed by mapping of nuclear lamina interactions. Nature 453: 948–951.

Hassan AH, Neely KE and Workman JL (2001) Histone acetyltransferase complexes stabilize swi/snf binding to promoter nucleosomes. Cell 104 (6): 817–827.

Henry KW, Wyce A, Lo WS, et al. (2003) Transcriptional activation via sequential histone H2B ubiquitylation and deubiquitylation, mediated by SAGA‐associated Ubp8. Genes and Development 17 (21): 2648–2663.

Hsu JY, Sun ZW, Li X, et al. (2000) Mitotic phosphorylation of histone H3 is governed by Ipl1/aurora kinase and Glc7/PP1 phosphatase in budding yeast and nematodes. Cell 102 (3): 279–291.

Huang S, Litt M and Felsenfeld G (2005) Methylation of histone H4 by arginine methyltransferase PRMT1 is essential in vivo for many subsequent histone modifications. Genes and Development 19 (16): 1885–1893.

Imhof A and Wolffe AP (1998) Transcription: gene control by targeted histone acetylation. Current Biology 8 (12): R422–R424. Review.

Jenuwein T and Allis CD (2001) Translating the histone code. Science 293 (5532): 1074–1080. Review.

Labrador M and Corces VG (2003) Phosphorylation of histone H3 during transcriptional activation depends on promoter structure. Genes and Development 17 (1): 43–58.

Lachner M, O'Carroll D, Rea S, et al. (2001) Methylation of histone H3 lysine 9 creates a binding site for HP1 proteins. Nature 410 (6824): 116–120.

Lieberman‐Aiden E, van Berkum NL, Williams L, et al. (2009) Comprehensive mapping of long‐range interactions reveals folding principles of the human genome. Science 326 (5950): 289–293.

Litt M, Qiu Y and Huang S (2009) Histone arginine methylations: their roles in chromatin dynamics and transcriptional regulation. Bioscience Reports 29 (2): 131–141.

Marshall WF, Fung JC and Sedat JW (1997) Deconstructing the nucleus: global architecture from local interactions. Current Opinion in Genetics and Development 7 (2): 259–263. Review.

Mizzen CA, Yang XJ, Kokubo T, et al. (1996) The TAF(II)250 subunit of TFIID has histone acetyltransferase activity. Cell 87 (7): 1261–1270.

Morey C, Da Silva NR, Perry P and Bickmore WA (2007) Nuclear reorganisation and chromatin decondensation are conserved, but distinct, mechanisms linked to Hox gene activation. Development 134 (5): 909–919.

Noordermeer D, Leleu M, Schorderet P, et al. (2014) Temporal dynamics and developmental memory of 3D chromatin architecture at Hox gene loci. eLife 3: e02557.

Nora EP, Lajoie BR, Schulz EG, et al. (2012) Spatial partitioning of the regulatory landscape of the X‐inactivation centre. Nature 485 (7398): 381–385.

Parada LA, McQueen PG and Misteli T (2004) Tissue‐specific spatial organization of genomes. Genome Biology 5 (7): R44.

Phillips‐Cremins JE, Sauria ME, Sanyal A, et al. (2013) Architectural protein subclasses shape 3D organization of genomes during lineage commitment. Cell 153 (6): 1281–1295.

Pope BD, Ryba T, Dileep V, et al. (2014) Topologically associating domains are stable units of replication‐timing regulation. Nature 515 (7527): 402–405.

Rothbart SB and Strahl BD (2014) Interpreting the language of histone and DNA modifications. Biochimica et Biophysica Acta 1839 (8): 627–643. Review.

Ryba T, Hiratani I, Lu J, et al. (2010) Evolutionarily conserved replication timing profiles predict long‐range chromatin interactions and distinguish closely related cell types. Genome Research 20 (6): 761–770.

Schoenfelder S, Sexton T, Chakalova L, et al. (2010) Preferential associations between co‐regulated genes reveal a transcriptional interactome in erythroid cells. Nature Genetics 42 (1): 53–61.

Seto E and Yoshida M (2014) Erasers of histone acetylation: the histone deacetylase enzymes. Cold Spring Harbor Perspectives in Biology 6 (4): a018713. Review.

Sexton T, Yaffe E, Kenigsberg E, et al. (2012) Three‐dimensional folding and functional organization principles of the Drosophila genome. Cell 148 (3): 458–472.

Shi Y, Lan F, Matson C, et al. (2004) Histone demethylation mediated by the nuclear amine oxidase homolog LSD1. Cell 119 (7): 941–953.

Shi Y, Lan F, Matson C, et al. (2007) Dynamic regulation of histone lysine methylation by demethylases. Molecular Cell 25 (1): 1–14. Review.

Tardat M, Brustel J, Kirsh O, et al. (2010) The histone H4 Lys 20 methyltransferase PR‐Set7 regulates replication origins in mammalian cells. Nature Cell Biology 12 (11): 1086–1093.

Therizols P, Illingworth RS, Courilleau C, et al. (2014) Chromatin decondensation is sufficient to alter nuclear organization in embryonic stem cells. Science 346 (6214): 1238–1242.

Tessarz P and Kouzarides T (2014) Histone core modifications regulating nucleosome structure and dynamics. Nature Reviews Molecular Cell Biology 15 (11): 703–708. Review.

Vitaliano‐Prunier A, Menant A, Hobeika M, et al. (2008) Ubiquitylation of the COMPASS component Swd2 links H2B ubiquitylation to H3K4 trimethylation. Nature Cell Biology 10 (11): 1365–1371.

Yen CY, Huang HW, Shu CW, et al. (2016) DNA methylation, histone acetylation and methylation of epigenetic modifications as a therapeutic approach for cancers. Cancer Letters 373 (2): 185–192. Review.

Zhang Y (2003) Transcriptional regulation by histone ubiquitination and deubiquitination. Genes and Development 17 (22): 2733–2740. Review.

Zink LM and Hake SB (2016) Histone variants: nuclear function and disease. Current Opinion in Genetics and Development 37: 82–89. Review.

Further Reading

Allis D, Jenuwein T and Reinberg D (2007) Epigenetics. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press.

Elgin SCR and Workman JL (2000) Chromatin Structure and Gene Expression, 2nd edn. Oxford, UK: Oxford University Press.

Gilbert DM and Fraser P (2015) Three dimensional organization of the nucleus: adding DNA sequences to the big picture. Genome Biology 16: 181 Special issue. DOI: 10.1186/s13059-015-0751-9.

Roger D Kornberg and Yahli Lorch (2007) Focus on Chromatin: Chromatin rules. Nature Structural and Molecular Biology 14: 986–988. DOI: 10.1038/nsmb1107-986-988.

Turner BM (2007) Chromatin and Gene Regulation: Mechanisms in Epigenetics. 10.1002/9780470750629

Van Steensel B and Dekker J (2010) Genomics tools for unraveling chromosome architecture. Nature Biotechnology 28 (10): 1089–1095.

Wolffe A (1998) Chromatin: Structure and Function, 3rd edn. London, UK: Academic Press.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Izard, Fanny, and Grimaud, Charlotte(Mar 2017) Chromatin Structure and Domains. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0005279.pub3]