Histone deacetylase 1 (HDAC1) is an

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...

that in humans is encoded by the ''HDAC1''

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

Function

Histone acetylation and deacetylation, catalyzed by multisubunit complexes, play a key role in the regulation of

eukaryotic Eukaryotes () are organisms whose cells have a nucleus. All animals, plants, fungi, and many unicellular organisms, are Eukaryotes. They belong to the group of organisms Eukaryota or Eukarya, which is one of the three domains of life. Bacte ...

gene expression. The protein encoded by this gene belongs to the histone deacetylase/acuc/apha family and is a component of the histone deacetylase complex. It also interacts with retinoblastoma tumor-suppressor protein and this complex is a key element in the control of cell proliferation and differentiation. Together with metastasis-associated protein-2

MTA2 MTA may refer to: Organizations Transportation * Metropolitan Transportation Authority, the public transport agency in the metropolitan area of New York City, United States * Metropolitan Transit Authority (disambiguation), which may refer to seve ...

, it deacetylates

p53 p53, also known as Tumor protein P53, cellular tumor antigen p53 (UniProt name), or transformation-related protein 53 (TRP53) is a regulatory protein that is often mutated in human cancers. The p53 proteins (originally thought to be, and often s ...

and modulates its effect on cell growth and apoptosis.

Model organisms

Model organism A model organism (often shortened to model) is a non-human species that is extensively studied to understand particular biological phenomena, with the expectation that discoveries made in the model organism will provide insight into the workin ...

s have been used in the study of HDAC1 function. A conditional

knockout mouse A knockout mouse, or knock-out mouse, is a genetically modified mouse (''Mus musculus'') in which researchers have inactivated, or "knocked out", an existing gene by replacing it or disrupting it with an artificial piece of DNA. They are importan ...

line, called ''Hdac1^{tm1a(EUCOMM)Wtsi}'' was generated as part of the

International Knockout Mouse Consortium The International Knockout Mouse Consortium (IKMC) is a scientific endeavour to produce a collection of mouse embryonic stem cell lines that together lack every gene in the genome, and then to distribute the cells to scientific researchers to crea ...

program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists — at the

Wellcome Trust Sanger Institute The Wellcome Sanger Institute, previously known as The Sanger Centre and Wellcome Trust Sanger Institute, is a non-profit British genomics and genetics research institute, primarily funded by the Wellcome Trust. It is located on the Wellcome G ...

. Male and female animals underwent a standardized

phenotypic screen In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology or physical form and structure, its developmental processes, its biochemical and physiological proper ...

to determine the effects of deletion. Twenty five tests were carried out and two

phenotypes In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology or physical form and structure, its developmental processes, its biochemical and physiological proper ...

were reported. A reduced number of

homozygous Zygosity (the noun, zygote, is from the Greek "yoked," from "yoke") () is the degree to which both copies of a chromosome or gene have the same genetic sequence. In other words, it is the degree of similarity of the alleles in an organism. Mo ...

mutant In biology, and especially in genetics, a mutant is an organism or a new genetic character arising or resulting from an instance of mutation, which is generally an alteration of the DNA sequence of the genome or chromosome of an organism. It ...

embryos were identified during gestation, and none survived until

weaning Weaning is the process of gradually introducing an infant human or another mammal to what will be its adult diet while withdrawing the supply of its mother's milk. The process takes place only in mammals, as only mammals produce milk. The infan ...

. The remaining tests were carried out on

heterozygous Zygosity (the noun, zygote, is from the Greek "yoked," from "yoke") () is the degree to which both copies of a chromosome or gene have the same genetic sequence. In other words, it is the degree of similarity of the alleles in an organism. Mo ...

mutant adult mice, and no significant abnormalities were observed in these animals.

Interactions

HDAC1 has been shown to

interact Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex traits. The organizati ...

with: *

Androgen receptor The androgen receptor (AR), also known as NR3C4 (nuclear receptor subfamily 3, group C, member 4), is a type of nuclear receptor that is activated by binding any of the androgenic hormones, including testosterone and dihydrotestosterone in th ...

, * BCL6, * BTG2, *

BUB1B Mitotic checkpoint serine/threonine-protein kinase BUB1 beta is an enzyme that in humans is encoded by the ''BUB1B'' gene. Also known as BubR1, this protein is recognized for its mitotic roles in the spindle assembly checkpoint (SAC) and kinetochor ...

, *

BUB1 Mitotic checkpoint serine/threonine-protein kinase BUB1 also known as BUB1 (budding uninhibited by benzimidazoles 1) is an enzyme that in humans is encoded by the ''BUB1'' gene. Bub1 is a serine/threonine protein kinase first identified in gen ...

, *

BUB3 Mitotic checkpoint protein BUB3 is a protein that in humans is encoded by the ''BUB3'' gene. Bub3 is a protein involved with the regulation of the Spindle Assembly Checkpoint (SAC); though BUB3 is non-essential in yeast, it is essential in hig ...

, * CBFA2T3, *

CDC20 The cell division cycle protein 20 homolog is an essential regulator of cell division that is encoded by the ''CDC20'' gene in humans. To the best of current knowledge its most important function is to activate the anaphase promoting complex (APC/ ...

, * CDH1, * CHD3, *

CHD4 Chromodomain-helicase-DNA-binding protein 4 is an enzyme that in humans is encoded by the ''CHD4'' gene. Function The product of this gene belongs to the SNF2/RAD54 helicase family. It represents the main component of the nucleosome remodeling ...

, *

COUP-TFII COUP-TFII (COUP transcription factor 2), also known as NR2F2 (nuclear receptor subfamily 2, group F, member 2) is a protein that in humans is encoded by the ''NR2F2'' gene. The COUP acronym stands for chicken ovalbumin upstream promoter. Functio ...

, *

CTBP1 C-terminal-binding protein 1 also known as CtBP1 is a protein that in humans is encoded by the ''CTBP1'' gene. CtBP1 is one of two CtBP proteins, the other protein being CtBP2. Function The CtBP1 protein was originally identified as a human prote ...

, *

DDX17 Probable ATP-dependent RNA helicase DDX17 (p72) is an enzyme that in humans is encoded by the ''DDX17'' gene. Function DEAD box proteins, characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD), are putative RNA helicases. They are implicat ...

, *

DDX5 Probable ATP-dependent RNA helicase DDX5 also known as DEAD box protein 5 or RNA helicase p68 is an enzyme that in humans is encoded by the ''DDX5'' gene. Function DEAD box proteins, characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD) ...

, *

DNMT3A DNA (cytosine-5)-methyltransferase 3A is an enzyme that catalyzes the transfer of methyl groups to specific CpG structures in DNA, a process called DNA methylation. The enzyme is encoded in humans by the DNMT3A gene. This enzyme is responsible f ...

, *

DNMT3L DNA (cytosine-5)-methyltransferase 3-like is an enzyme that in humans is encoded by the ''DNMT3L'' gene. Function CpG methylation is an epigenetic modification that is important for embryonic development, imprinting, and X-chromosome inactiv ...

, *

Death-associated protein 6 Death-associated protein 6 also known as Daxx is a protein that in humans is encoded by the ''DAXX'' gene. Function Daxx, a Death domain-associated protein, was first discovered through its cytoplasmic interaction with the classical death rece ...

, * EED, *

EVI1 MDS1 and EVI1 complex locus protein EVI1 (MECOM) also known as ecotropic virus integration site 1 protein homolog (EVI-1) or positive regulatory domain zinc finger protein 3 (PRDM3) is a protein that in humans is encoded by the ''MECOM'' gene. EVI ...

, *

EZH2 Enhancer of zeste homolog 2 (EZH2) is a histone-lysine N-methyltransferase enzyme ( EC 2.1.1.43) encoded by gene, that participates in histone methylation and, ultimately, transcriptional repression. EZH2 catalyzes the addition of methyl groups ...

, *

FKBP3 FK506-binding protein 3 also known as FKBP25 is a protein that in humans is encoded by the ''FKBP3'' gene. Function The protein encoded by this gene is a member of the immunophilin protein family, which play a role in immunoregulation and basi ...

, *

GATA1 GATA-binding factor 1 or GATA-1 (also termed Erythroid transcription factor) is the founding member of the GATA family of transcription factors. This protein is widely expressed throughout vertebrate species. In humans and mice, it is encoded by ...

, *

HMG20B SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily E member 1-related is a protein that in humans is encoded by the ''HMG20B'' gene. Interactions HMG20B has been shown to interact with: * BRCA2 ''BRCA2'' and ...

, *

HSPA4 Heat shock 70 kDa protein 4 is a protein that in humans is encoded by the ''HSPA4'' gene. The protein encoded by this gene was originally suggested to be a member of the heat shock protein 70 family. However it is now known that human HSPA4 is a ...

, *

HUS1 Checkpoint protein HUS1 is a protein that in humans is encoded by the ''HUS1'' gene. Function The protein encoded by this gene is a component of an evolutionarily conserved, genotoxin-activated checkpoint complex that is involved in the cell cy ...

, *

Histone deacetylase 2 Histone deacetylase 2 (HDAC2) is an enzyme that in humans is encoded by the ''HDAC2'' gene. It belongs to the histone deacetylase class of enzymes responsible for the removal of acetyl groups from lysine residues at the N-terminal region of the co ...

, *

Homeobox protein TGIF1 Homeobox protein TGIF1 is a protein that, in humans, is encoded by the ''TGIF1'' gene. Alternative splicing has been observed at this locus and eight variants, encoding four distinct isoforms, are described. Function The protein encoded by thi ...

, *

Host cell factor C1 Host cell factor 1 (HCFC1, HCF1, or HCF-1), also known as VP16-accessory protein, is a protein that in humans is encoded by the ''HCFC1'' gene. Structure HCF1 is a member of the highly conserved host cell factor family and encodes a protein wi ...

, *

IFRD1 Interferon-related developmental regulator 1 is a protein that in humans is encoded by the ''IFRD1'' gene. The gene is expressed mostly in neutrophils, skeletal and cardiac muscle, the brain, and the pancreas. The rat and the mouse homolog genes ...

, *

IKZF1 DNA-binding protein Ikaros also known as Ikaros family zinc finger protein 1 is a protein that in humans is encoded by the ''IKZF1'' gene. Ikaros - transcription factor Ikaros is a transcription factor that is encoded by the ''IKZF'' genes of ...

, *

ING1 Inhibitor of growth protein 1 is a protein that in humans is encoded by the ''ING1'' gene. Function This gene encodes a tumor suppressor protein that can induce cell growth arrest and apoptosis. The encoded protein is a nuclear protein that ph ...

, *

MBD3 Methyl-CpG-binding domain protein 3 is a protein that in humans is encoded by the ''MBD3'' gene. Function DNA methylation is the major modification of eukaryotic genomes and plays an essential role in mammalian development. Human proteins ME ...

, *

MIER1 Mesoderm induction early response protein 1 is a protein that in humans is encoded by the ''MIER1'' gene. Interactions MIER1 has been shown to interact Advocates for Informed Choice, doing business as, dba interACT or interACT Advocates f ...

, * MLL, *

MTA1 Metastasis-associated protein MTA1 is a protein that in humans is encoded by the ''MTA1'' gene. MTA1 is the founding member of the MTA family of genes. MTA1 is primarily localized in the nucleus but also found to be distributed in the extra-nucl ...

, *

Mad1 Mad1 is a non-essential protein which in yeast has a function in the spindle assembly checkpoint (SAC). This checkpoint monitors chromosome attachment to spindle microtubules and prevents cells from starting anaphase until the spindle is built up ...

, * Mdm2, *

Methyl-CpG-binding domain protein 2 Methyl-CpG-binding domain protein 2 is a protein that in humans is encoded by the ''MBD2'' gene. Function DNA methylation is the major modification of eukaryotic genomes and plays an essential role in mammalian development. Human proteins MECP2 ...

, *

Mothers against decapentaplegic homolog 2 Mothers against decapentaplegic homolog 2 also known as SMAD family member 2 or SMAD2 is a protein that in humans is encoded by the ''SMAD2'' gene. MAD homolog 2 belongs to the SMAD, a family of proteins similar to the gene products of the ''Dros ...

, *

MyoD MyoD, also known as myoblast determination protein 1, is a protein in animals that plays a major role in regulating muscle differentiation. MyoD, which was discovered in the laboratory of Harold M. Weintraub, belongs to a family of proteins know ...

, *

NFKB1 Nuclear factor NF-kappa-B p105 subunit is a protein that in humans is encoded by the ''NFKB1'' gene. This gene encodes a 105 kD protein which can undergo cotranslational processing by the 26S proteasome to produce a 50 kD protein. The 105 kD prot ...

, *

Nuclear receptor co-repressor 2 The nuclear receptor co-repressor 2 () is a transcriptional coregulatory protein that contains several nuclear receptor-interacting domains. In addition, NCOR2 appears to recruit histone deacetylases to DNA promoter regions. Hence NCOR2 assists ...

, *

P21 p21Cip1 (alternatively p21Waf1), also known as cyclin-dependent kinase inhibitor 1 or CDK-interacting protein 1, is a cyclin-dependent kinase inhibitor (CKI) that is capable of inhibiting all cyclin/CDK complexes, though is primarily associated ...

, *

PCNA Proliferating cell nuclear antigen (PCNA) is a DNA clamp that acts as a processivity factor for DNA polymerase δ in eukaryotic cells and is essential for replication. PCNA is a homotrimer and achieves its processivity by encircling the DNA, wh ...

, *

PHF21A PHD finger protein 21A is a protein that in humans is encoded by the ''PHF21A'' gene. Function BHC80 is a component of a BRAF35 (MIM 605535)/histone deacetylase (HDAC; see MIM 601241) complex (BHC) that mediates repression of neuron-specific g ...

, *

Prohibitin Prohibitin, also known as PHB, is a protein that in humans is encoded by the ''PHB'' gene. The ''Phb'' gene has also been described in animals, fungi, plants, and unicellular eukaryotes. Prohibitins are divided in two classes, termed Type-I and Ty ...

, *

Promyelocytic leukemia protein Promyelocytic leukemia protein (PML) (also known as MYL, RNF71, PP8675 or TRIM19) is the protein product of the PML gene. PML protein is a tumor suppressor protein required for the assembly of a number of nuclear structures, called PML-nuclear bod ...

, *

RAD9A Cell cycle checkpoint control protein RAD9A is a protein that in humans is encoded by the ''RAD9A'' gene.''Rad9'' has been shown to induce G2 arrest in the cell cycle in response to DNA damage in yeast cells. ''Rad9'' was originally found in buddin ...

, *

RBBP4 #REDIRECT RBBP4 {{R from other capitalization ...

, *

RBBP7 Histone-binding protein RBBP7 is a protein that in humans is encoded by the ''RBBP7'' gene. Function This protein is a ubiquitously expressed nuclear protein and belongs to a highly conserved subfamily of WD-repeat proteins. It is found among ...

, *

RCOR1 REST corepressor 1 also known as CoREST is a protein that in humans is encoded by the ''RCOR1'' gene. Function This gene encodes a protein that is well-conserved, downregulated at birth, and with a specific role in determining neural cell dif ...

, *

RELA Transcription factor p65 also known as nuclear factor NF-kappa-B p65 subunit is a protein that in humans is encoded by the ''RELA'' gene. RELA, also known as p65, is a REL-associated protein involved in NF-κB heterodimer formation, nuclear tra ...

, *

RFC1 Replication factor C subunit 1 is a protein that in humans is encoded by the ''RFC1'' gene. Function The protein encoded by this gene is the large subunit of replication factor C, which is a five subunit DNA polymerase accessory protein. Replic ...

, *

Retinoblastoma protein The retinoblastoma protein (protein name abbreviated pRb; gene name abbreviated ''Rb'', ''RB'' or ''RB1'') is a proto-oncogenic tumor suppressor protein that is dysfunctional in several major cancers. One function of pRb is to prevent excessive ...

, *

Retinoblastoma-like protein 1 Retinoblastoma-like 1 (p107), also known as RBL1, is a protein that in humans is encoded by the ''RBL1'' gene. Function The protein encoded by this gene is similar in sequence and possibly function to the product of the retinoblastoma 1 ( RB1 ...

, *

Retinoblastoma-like protein 2 Retinoblastoma-like protein 2 is a protein that in humans is encoded by the ''RBL2'' gene. Interactions Retinoblastoma-like protein 2 has been shown to interact with: * BRCA1, * BRF1 * C-Raf, * Cyclin E1, * Cyclin-dependent kinase 2, ...

, *

SAP30 Sin3A-associated protein, 30kDa, also known as SAP30, is a protein which in humans is encoded by the SAP30 gene. Function Histone acetylation plays a key role in the regulation of eukaryotic gene expression. Histone acetylation and deacetylatio ...

, *

SATB1 SATB1 (special AT-rich sequence-binding protein-1) is a protein which in humans is encoded by the ''SATB1'' gene. Function SATB1, the global chromatin organizer and transcription factor, has emerged as a key factor integrating higher-order chro ...

, * SIN3A, *

SIN3B Paired amphipathic helix protein Sin3b is a protein that in humans is encoded by the ''SIN3B'' gene. Interactions SIN3B has been shown to interact with HDAC1, Zinc finger and BTB domain-containing protein 16, SUDS3 and IKZF1. See also * Tra ...

, *

SPEN Msx2-interacting protein is a protein that in humans is encoded by the ''SPEN'' gene. This gene encodes a hormone inducible transcriptional repressor. Repression of transcription by this gene product can occur through interactions with other rep ...

, * SUDS3, * SUV39H1, *

Sp1 transcription factor Transcription factor Sp1, also known as specificity protein 1* is a protein that in humans is encoded by the SP1 gene. Function The protein encoded by this gene is a zinc finger transcription factor that binds to GC-rich motifs of many promote ...

, *

TOP2A DNA topoisomerase IIα is a human enzyme encoded by the ''TOP2A'' gene. Topoisomerase IIα relives topological DNA stress during transcription, condenses chromosomes, and separates chromatids. It catalyzes the transient breaking and rejoining of ...

, *

TOP2B DNA topoisomerase 2-beta is an enzyme that in humans is encoded by the ''TOP2B'' gene. Function This gene encodes a DNA topoisomerase, an enzyme that controls and alters the topologic states of DNA during transcription. This nuclear enzyme is ...

, and *

Zinc finger and BTB domain-containing protein 16 Zinc finger and BTB domain-containing protein 16 is a protein that in humans is encoded by the ''ZBTB16'' gene. Function This gene is a member of the Krueppel C2H2-type zinc-finger protein family and encodes a zinc finger transcription factor ...

References

External links

* {{Portal bar, Biology, border=no EC 3.5.1 Genes mutated in mice Δ1

Function

Model organisms

Interactions

See also

References

Further reading

External links