Sunday 13 July 2003
Definition: Chromatin is the DNA/protein/RNA complex extracted from eukaryotic lysed interphase nuclei. Just which of the multitudinous substances present in a nucleus will constitute a part of the extracted material will depend in part on the technique each researcher uses. Furthermore, the composition and properties of chromatin vary from one cell type to the another, during development of a specific cell type, and at different stages in the cell cycle.
Chromatin is found inside the nucleus of a cell. Chromatin is the structural building block of a chromosome and consists of a complex of DNA and protein in eukaryotic cells. It can be made visible by staining, hence its name, which literally means coloured material.
The nucleic acids are generally in the form of double-stranded DNA - i.e. the famous DNA-double helix. The major proteins involved in chromatin are histone proteins but other non-histone chromosomal proteins are prominent too.
DNA is packaged into chromatin thereby constraining the size of the molecule and allowing the cell to control expression of the chromatin packaged genes.
Changes in chromatin structure are affected mainly by methylation (DNA and proteins) and acetylation (proteins). Chromatin structure is also of importance to DNA replication and DNA repair.
Dynamic regulation of chromatin structure is thought to be a prerequisite for nuclear functions that require accessibility to DNA such as replication, transcription and DNA repair.
Simplistically, there are three major levels of chromatin organization:
nucleosome - "beads on a string"
30 nm condensed chromatin fiber consisting of nucleosome arrays in their most compact form
The hierarchy continues with increasing DNA-packaging density until the metaphase chromosome is attained.
The human genome contains 23 000 genes that must be expressed in specific cells at precise times. Cells manage gene expression by wrapping DNA around clusters (octamers) of globular histone proteins to form nucleosomes.
These nucleosomes of DNA and histones are organized into chromatin. Changes to the structure of chromatin influence gene expression: genes are inactivated (switched off) when the chromatin is condensed (silent), and they are expressed (switched on) when chromatin is open (active).
These dynamic chromatin states are controlled by reversible epigenetic patterns of DNA methylation and histone modifications.
Enzymes involved in this process include DNA methyltransferases (DNMTs), histone deacetylases (HDACs), histone acetylases, histone methyltransferases and the methyl-binding domain protein MECP2.
Alterations in these normal epigenetic patterns can deregulate patterns of gene expression, which results in profound and diverse clinical outcomes.
Sperm cell chromatin
Sperm cell chromatin is an exception to the above. During spermiogenesis, the spermatid’s chromatin is remodelled into a more tightly packaged, compact, almost crystal-like structure. This process is associated with the cessation of transcription and involves nuclear protein exchange. The histones are mostly displaced, and replaced by protamines, small, arginine-rich proteins.
- euchromatin is a type of chromatin that is rich in gene concentration (contrast this to heterochromatin). This type of chromatin generally appears as light-colored bands when stained in GTG banding and observed under an optical microscope. In contrast to heterochromatin, euchromatin is not tightly wrapped around histones meaning that genes within the region are frequently transcribed to messenger RNA (mRNA) in the cell.
Pathology (chromatin diseases)
chromatin remodeling disorders
- Williams-Beuren syndrome
- rhabdoid tumor syndrome
pathology of chromatin assembly
- Rett syndrome
chromatin remodelling and chromatin remodeling complexes
Kwon CS, Wagner D. Unwinding chromatin for development and growth: a few genes at a time. Trends Genet. 2007 Aug;23(8):403-12. PMID: #17566593#
Ruthenburg AJ, Li H, Patel DJ, Allis CD. Multivalent engagement of chromatin modifications by linked binding modules. Nat Rev Mol Cell Biol. 2007 Dec;8(12):983-94. PMID: #18037899#
Ooi L, Wood IC. Chromatin crosstalk in development and disease: lessons from REST. Nat Rev Genet. 2007 Jul;8(7):544-54. PMID: #17572692#
Huebert DJ, Bernstein BE. Genomic views of chromatin. Curr Opin Genet Dev. 2005 Oct;15(5):476-81. PMID: #16099159#
Sproul D, Gilbert N, Bickmore WA. The role of chromatin structure in regulating the expression of clustered genes. Nat Rev Genet. 2005 Oct;6(10):775-81. PMID: #16160692#
Donaldson AD. Shaping time: chromatin structure and the DNA replication programme. Trends Genet. 2005 Aug;21(8):444-9. PMID: #15951049#
Croce LD. Chromatin modifying activity of leukaemia associated fusion proteins. Hum Mol Genet. 2005 Apr 15;14 Spec No 1:R77-84. PMID: #15809276#
Chandler VL, Stam M. Chromatin conversations: mechanisms and implications of paramutation. Nat Rev Genet. 2004 Jul;5(7):532-44. PMID: #15211355#
Jones DR, Divecha N. Linking lipids to chromatin. Curr Opin Genet Dev. 2004 Apr;14(2):196-202. PMID: #15196467#
Bickmore WA, van der Maarel SM. Perturbations of chromatin structure in human genetic disease: recent advances. Hum Mol Genet. 2003 Oct 15;12 Spec No 2:R207-13. PMID: #12915455#
Hendrich B, Bickmore W. Human diseases with underlying defects in chromatin structure and modification. Hum Mol Genet. 2001 Oct 1;10(20):2233-42. PMID: #11673406#