Chromatin Remodeling
Our nucleosomal DNA is exposed to constant changes in structure, composition and positioning of nucleosomes in order to expose entire regions of a chromosome or render them inaccessible instead. This process is called chromatin remodeling - the highest level of transcription regulation in eukaryotes.
Covalent histone modifications by specific enzymes, and ATP-dependent chromatin remodeling complexes which move, eject or restructure nucleosomes are responsible for chromatin remodelling. remodeling of chromatin imparts an epigenetic regulatory role in several key biological processes for example DNA damage repair or apoptosis.
Antibodies for Chromatin Remodeling
Covalent Histone-Modifying Complexes
Specific protein complexes, like histone acetyltransferases (HATs), deacetylases, methyltransferases, and kinases, known as histone-modifying complexes catalyze addition or removal of various chemical elements on histones. Such modifications affect the binding affinity between histones and DNA, and thus loosening or tightening the condensed DNA wrapped around histones, e.g., Methylation of specific lysine residues in H3 and H4 causes further condensation of DNA around histones, and thereby prevents binding of transcription factors to the DNA that lead to gene repression. On the contrary, histone acetylation relaxes chromatin condensation and exposes DNA for TF binding, leading to increased gene expression.
ATP-Dependent Chromatin Remodeling
There are at least five families of chromatin remodelers in eukaryotes: SWI/SNF, ISWI, NuRD/Mi-2/CHD, INO80 and SWR1 with first two remodelers being very well studied so far, especially in the yeast model. Although all of remodelers share common ATPase domain, their functions are specific based on several biological processes. This is due to the fact that each remodeler complex has unique protein domains (Helicase, bromodomain, etc.) in their catalytic ATPase region and also has different recruited subunits.
The ISWI-family remodelers have been shown to play central roles in chromatin assembly after DNA replication and maintenance of higher-order chromatin structures. They organize nucleosome into proper bundle form and create equal spacing between nucleosomes, whereas SWI/SNF remodelers disorder nucleosomes.
INO80 and SWI/SNF-family remodelers participate in DNA double-strand break (DSB) repair and nucleotide-excision repair (NER) and thereby plays crucial role in TP53 mediated DNA-damage response. NuRD/Mi-2/CHD remodeling complexes primarily mediate transcriptional repression in the nucleus and are required for the maintenance of pluripotency of embryonic stem cells. Enzymes.
DNA Damage Repair
The relaxation appears to be initiated by PARP1, whose accumulation at DNA damage is half complete by 1.6 seconds after DNA damage occurs. This is quickly followed by accumulation of chromatin remodeler Alc1, which has an ADP-ribose–binding domain, allowing it to be quickly attracted to the product of PARP1. PARP1 action at the site of a double-strand break allows recruitment of the two DNA repair enzymes MRE11 and NBS1. The fast initial chromatin relaxation upon DNA damage (with rapid initiation of DNA repair) is followed by a slow recondensation, with chromatin recovering a compaction state close to its predamage level in about 20 minutes
Antibodies for DNA Damage Repair
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References
- Cassani C. et al. Structurally distinct Mre11 domains mediate MRX functions in resection, end-tethering and DNA damage resistance. (2018) doi: 10.1093/nar/gky086
- Kijas A. et al. ATM-dependent phosphorylation of MRE11 controls extent of resection during homology directed repair by signalling through Exonuclease 1. (2015) doi: 10.1093/nar/gkv754
- Moore S. et al. Transcription Factors and DNA Repair Enzymes Compete for Damaged Promoter Sites. J Biol Chem (2016).10.1074/jbc.M115.672733
- Torigoe S. et al. ATP-dependent chromatin assembly is functionally distinct from chromatin remodeling. eLife (2013).doi: 10.7554/eLife.00863
- Hota K. et al. ATP-dependent chromatin remodeling during mammalian development. Development (2016).doi: 10.1242/dev.128892
