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Chromatin is a complex of DNA and protein found in eukaryotic cells. Its primary function is packaging long DNA molecules into more compact, denser structures. This prevents the strands from becoming tangled and also plays important roles in reinforcing the DNA during cell division, preventing DNA damage, and regulating gene expression and DNA replication. During mitosis and meiosis, chromatin facilitates proper segregation of the chromosomes in anaphase; the characteristic shapes of chromosomes visible during this stage are the result of DNA being coiled into highly condensed chromatin.
A nucleosome is the basic structural unit of DNA packaging in eukaryotes. The structure of a nucleosome consists of a segment of DNA wound around eight histone proteins and resembles thread wrapped around a spool. The nucleosome is the fundamental subunit of chromatin. Each nucleosome is composed of a little less than two turns of DNA wrapped around a set of eight proteins called histones, which are known as a histone octamer. Each histone octamer is composed of two copies each of the histone proteins H2A, H2B, H3, and H4.
Histone acetyltransferases (HATs) are enzymes that acetylate conserved lysine amino acids on histone proteins by transferring an acetyl group from acetyl-CoA to form ε-N-acetyllysine. DNA is wrapped around histones, and, by transferring an acetyl group to the histones, genes can be turned on and off. In general, histone acetylation increases gene expression.
A histone octamer is the eight protein complex found at the center of a nucleosome core particle. It consists of two copies of each of the four core histone proteins. The octamer assembles when a tetramer, containing two copies of both H3 and H4, complexes with two H2A/H2B dimers. Each histone has both an N-terminal tail and a C-terminal histone-fold. Both of these key components interact with DNA in their own way through a series of weak interactions, including hydrogen bonds and salt bridges. These interactions keep the DNA and histone octamer loosely associated and ultimately allow the two to re-position or separate entirely.
In molecular biology, SWI/SNF, is a subfamiliy of ATP-dependent chromatin remodeling complexes, which is found in eukaryotes. In other words, it is a group of proteins that associate to remodel the way DNA is packaged. This complex is composed of several proteins – products of the SWI and SNF genes, as well as other polypeptides. It possesses a DNA-stimulated ATPase activity that can destabilize histone-DNA interactions in reconstituted nucleosomes in an ATP-dependent manner, though the exact nature of this structural change is unknown. The SWI/SNF subfamily provides crucial nucleosome rearrangement, which is seen as ejection and/or sliding. The movement of nucleosomes provides easier access to the chromatin, allowing genes to be activated or repressed.
Histone H2A is one of the five main histone proteins involved in the structure of chromatin in eukaryotic cells.
In molecular biology and genetics, transcription coregulators are proteins that interact with transcription factors to either activate or repress the transcription of specific genes. Transcription coregulators that activate gene transcription are referred to as coactivators while those that repress are known as corepressors. The mechanism of action of transcription coregulators is to modify chromatin structure and thereby make the associated DNA more or less accessible to transcription. In humans several dozen to several hundred coregulators are known, depending on the level of confidence with which the characterisation of a protein as a coregulator can be made. One class of transcription coregulators modifies chromatin structure through covalent modification of histones. A second ATP dependent class modifies the conformation of chromatin.
Chromatin remodeling is the dynamic modification of chromatin architecture to allow access of condensed genomic DNA to the regulatory transcription machinery proteins, and thereby control gene expression. Such remodeling is principally carried out by 1) covalent histone modifications by specific enzymes, e.g., histone acetyltransferases (HATs), deacetylases, methyltransferases, and kinases, and 2) ATP-dependent chromatin remodeling complexes which either move, eject or restructure nucleosomes. Besides actively regulating gene expression, dynamic remodeling of chromatin imparts an epigenetic regulatory role in several key biological processes, egg cells DNA replication and repair; apoptosis; chromosome segregation as well as development and pluripotency. Aberrations in chromatin remodeling proteins are found to be associated with human diseases, including cancer. Targeting chromatin remodeling pathways is currently evolving as a major therapeutic strategy in the treatment of several cancers.
Paired amphipathic helix protein Sin3a is a protein that in humans is encoded by the SIN3A gene.
AT-rich interactive domain-containing protein 1A is a protein that in humans is encoded by the ARID1A gene.
Chromodomain-helicase-DNA-binding protein 3 is an enzyme that in humans is encoded by the CHD3 gene.
Chromodomain-helicase-DNA-binding protein 4 is an enzyme that in humans is encoded by the CHD4 gene.
Chromodomain-helicase-DNA-binding protein 1 is a chromatin remodeler that in humans is encoded by the CHD1 gene.
Lysine-specific demethylase 5C is an enzyme that in humans is encoded by the KDM5C gene. KDM5C belongs to the alpha-ketoglutarate-dependent hydroxylase superfamily.
In the field of molecular biology, the Mi-2/NuRDcomplex, is a group of associated proteins with both ATP-dependent chromatin remodeling and histone deacetylase activities. As of 2007, Mi-2/NuRD was the only known protein complex that couples chromatin remodeling ATPase and chromatin deacetylation enzymatic functions.
Nucleoplasmin, the first identified molecular chaperone is a thermostable acidic protein with a pentameric structure. The protein was first isolated from Xenopus species
Memory is commonly referred to as the ability to encode, store, retain and subsequently recall information and past experiences in the human brain. This process involves many proteins, one of which is the Histone-binding protein RbAp48, encoded by the RBBP4 gene in humans.
H3K4me3 is an epigenetic modification to the DNA packaging protein Histone H3. It is a mark that indicates the tri-methylation at the 4th lysine residue of the histone H3 protein and often involved in the regulation of gene expression. The name denotes the addition of three methyl groups (trimethylation) to the lysine 4 on the histone H3 protein.
The INO80 subfamily of chromatin remodeling complexes are ATPases, and includes the INO80 and SWR1 complexes.
Chromodomain helicase DNA-binding (CHD) proteins are a subfamily of ATP-dependent chromatin remodeling complexes (remodelers). All remodelers fall under the umbrella of RNA/DNA helicase superfamily 2. In yeast, CHD complexes are primarily responsible for nucleosome assembly and organization. These complexes play an additional role in multicellular eukaryotes, assisting in chromatin access and nucleosome editing.
References
- ↑ Horton JR, Elgar SJ, Khan SI, Zhang X, Wade PA, Cheng X (June 2007). "Structure of the SANT domain from the Xenopus chromatin remodeling factor ISWI". Proteins. 67 (4): 1198–202. doi:10.1002/prot.21352. PMC 2688785 . PMID 17377988.
- ↑ Boyer LA, Latek RR, Peterson CL (February 2004). "The SANT domain: a unique histone-tail-binding module?". Nature Reviews. Molecular Cell Biology. 5 (2): 158–63. doi:10.1038/nrm1314. PMID 15040448. S2CID 40665323.