Chromodomain-helicase-DNA-binding protein 8 is an enzyme that in humans is encoded by the CHD8 gene. [5] [6]
Chromodomain-helicase-DNA-binding protein 8 is an enzyme that in humans is encoded by the CHD8 gene. [5] [6]
The gene CHD8 encodes the protein chromodomain helicase DNA binding protein 8, [7] which is a chromatin regulator enzyme that is essential during fetal development. [8] CHD8 is an ATP dependent enzyme. [9]
The protein contains an Snf2 helicase domain that is responsible for the hydrolysis of ATP to ADP. [9] CHD8 encodes for a DNA helicase that function as a transcription repressor by remodeling chromatin structure by altering the position of nucleosomes. [8] CHD8 negatively regulates Wnt signaling. [10] Wnt signaling is important in the vertebrate early development and morphogenesis. It is believed that CHD8 also recruits the linker histone H1 and causes the repression of β-catenin and p53 target genes. [7] The importance of CHD8 can be observed in studies where CHD8-knockout mice died after 5.5 embryonic days because of widespread p53 induced apoptosis. [7]
Recently CD8 has been asscociated to the regulation of long non-coding RNAs (lncRNAs), [11] and the regulation of X chromosome inactivation (XCI) initiation, via regulation of Xist long non-coding RNA, the master regulator of XCI, though competitive binding to Xist regulatory regions. [12]
Mutations in this gene have been linked to a subset of autism [13] cases in human and mouse models. [14]
Mutations in CHD8 could lead to upregulation of β-catenin-regulated genes, in some part of the brain this upregulation can cause brain overgrowth also known as macrocephaly, which occurs in 15-35% of autistic children. [8]
Some studies have determined the role of CHD8 in autism spectrum disorder (ASD). [8] CHD8 expression significantly increases during human mid-fetal development. [7] The chromatin remodeling activity and its interaction with transcriptional regulators have shown to play an important role in ASD aetiology. [15] The developing mammalian brain has a conserved CHD8 target regions that are associated with ASD risk genes. [8] The knockdown of CHD8 in human neural stem cells results in dysregulation of ASD risk genes that are targeted by CHD8. [16]
S phase (Synthesis Phase) is the phase of the cell cycle in which DNA is replicated, occurring between G1 phase and G2 phase. Since accurate duplication of the genome is critical to successful cell division, the processes that occur during S-phase are tightly regulated and widely conserved.
The family of heterochromatin protein 1 (HP1) consists of highly conserved proteins, which have important functions in the cell nucleus. These functions include gene repression by heterochromatin formation, transcriptional activation, regulation of binding of cohesion complexes to centromeres, sequestration of genes to the nuclear periphery, transcriptional arrest, maintenance of heterochromatin integrity, gene repression at the single nucleosome level, gene repression by heterochromatization of euchromatin, and DNA repair. HP1 proteins are fundamental units of heterochromatin packaging that are enriched at the centromeres and telomeres of nearly all eukaryotic chromosomes with the notable exception of budding yeast, in which a yeast-specific silencing complex of SIR proteins serve a similar function. Members of the HP1 family are characterized by an N-terminal chromodomain and a C-terminal chromoshadow domain, separated by a hinge region. HP1 is also found at some euchromatic sites, where its binding can correlate with either gene repression or gene activation. HP1 was originally discovered by Tharappel C James and Sarah Elgin in 1986 as a factor in the phenomenon known as position effect variegation in Drosophila melanogaster.
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.
Transcription activator BRG1 also known as ATP-dependent chromatin remodeler SMARCA4 is a protein that in humans is encoded by the SMARCA4 gene.
High-mobility group protein HMG-I/HMG-Y is a protein that in humans is encoded by the HMGA1 gene.
SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 5 is a protein that in humans is encoded by the SMARCA5 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.
SATB1 is a protein which in humans is encoded by the SATB1 gene.
Chromodomain-helicase-DNA-binding protein 4 is an enzyme that in humans is encoded by the CHD4 gene.
Eukaryotic initiation factor 4A-I is a 46 kDa cytosolic protein that, in humans, is encoded by the EIF4A1 gene, which is located on chromosome 17. It is the most prevalent member of the eIF4A family of ATP-dependant RNA helicases, and plays a critical role in the initiation of cap-dependent eukaryotic protein translation as a component of the eIF4F translation initiation complex. eIF4A1 unwinds the secondary structure of RNA within the 5'-UTR of mRNA, a critical step necessary for the recruitment of the 43S preinitiation complex, and thus the translation of protein in eukaryotes. It was first characterized in 1982 by Grifo, et al., who purified it from rabbit reticulocyte lysate.
K(lysine) acetyltransferase 8 (KAT8) is an enzyme that in humans is encoded by the KAT8 gene.
The Chromodomain-Helicase DNA-binding 1 is a protein that, in humans, is encoded by the CHD1 gene. CHD1 is a chromatin remodeling protein that is widely conserved across many eukaryotic organisms, from yeast to humans. CHD1 is named for three of its protein domains: two tandem chromodomains, its ATPase catalytic domain, and its DNA-binding domain.
JADE1 is a protein that in humans is encoded by the JADE1 gene.
Chromodomain-helicase-DNA-binding protein 5 is an enzyme that in humans is encoded by the CHD5 gene. It is a part of the CHD subfamily of ATP-dependent chromatin remodeling complexes.
Chromodomain-helicase-DNA-binding protein 9 is an enzyme that in humans is encoded by the CHD9 gene.
Chromodomain-helicase-DNA-binding protein 1-like (ALC1) is an enzyme that in humans is encoded by the CHD1L gene. It has been implicated in chromatin remodeling and DNA relaxation process required for DNA replication, repair and transcription. The ALC1 comprises ATPase domain and macro domain. On the basis of homology within the ATPase domain, ALC1 belongs to Snf2 family.
Chromodomain-helicase-DNA-binding protein 2 is an enzyme that in humans is encoded by the CHD2 gene.
Reptin is a tumor repressor protein that is a member of the ATPases Associated with various cellular Activities (AAA+) helicase family and regulates KAI1. Desumoylation of reptin alters the repressive function of reptin and its association with HDAC1. The sumoylation status of reptin modulates the invasive activity of cancer cells with metastatic potential. Reptin was reported in 2010 to be a good marker for metastasis. Another name for reptin, RuvB-like 2 comes from its similarity to RuvB, an ATP-dependent helicase found in bacteria. Reptin is highly conserved, being found in yeast, drosophila, and humans. It presents itself as a member of a number of different protein complexes, most of which function in chromatin modification, including PRC1, TIP60/NuA4 and INO80. Hence, it also has the names INO80J, TIP48, and TIP49B. In the majority of its functions, reptin is paired with a very similar protein, pontin (RUVBL1).
Chromodomain helicase DNA-binding (CHD) proteins is 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.
PDB gallery | |
|---|---|
|
