JARID1A
Encyclopedia
Lysine-specific demethylase 5A is an enzyme
that in humans is encoded by the KDM5A gene
.
The Drosophila homolog, LID, was found to be an H3K4 histone demethylase
that binds to c-Myc
. It was recently renamed to Lysine Demethylase 5A (KDM5A).
Enzymatically can be designated as a trimethyllysine dioxygenase
. (EC 1.14.11.8)
with Estrogen receptor alpha
, LMO2
and Retinoblastoma protein
.
JARID1A is a major component of the circadian clock, the upregulation of which at the end of the sleep phase blocks HDAC1 activity. Blocking HDAC1 activity results in an upregulation of CLOCK and BMAL1 and consequent upregulation of PER proteins. The PSF (polypyrimidine tract-binding protein-associated splicing factor) within the PER complex recruits SIN3A, a scaffold for assembly of transcriptional inhibitory complexes and rhythmically delivers histone deacetylases to the Per1 promoter, which repress Per1 transcription.[PMID 21960634] [PMID 21680841]
Knockdown of JARID1A promoted osteogenic differentiation of human adipose-derived stromal cells in vitro and in vivo and resulted in marked increases of mRNA expression of osteogenesis-associated genes such as alkaline phosphatase (ALP), osteocalcin (OC), and osterix (OSX). RBP2 was shown to occupy the promoters of OSX and OC to maintain the level of the H3K4me3 mark by chromatin immunoprecipitation assays. RBP2 was also physically and functionally associated with RUNX2, an essential transcription factor that governed osteoblastic differentiation. RUNX2 knockdown impaired the repressive activity of RBP2 in osteogenic differentiation of human adipose-derived stromal cells. [PMID 21604327]
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
that in humans is encoded by the KDM5A gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
.
The Drosophila homolog, LID, was found to be an H3K4 histone demethylase
Demethylase
Demethylases are enzymes that remove methyl groups from proteins and other substances. They are used in a variety of processes, such as in chemotaxis signal transduction.-Hydrolytic demethylation:A good example of a demethylase is the activated Demethylases are enzymes that remove methyl (CH3-)...
that binds to c-Myc
Myc
Myc is a regulator gene that codes for a transcription factor. In the human genome, Myc is located on chromosome 8 and is believed to regulate expression of 15% of all genes through binding on Enhancer Box sequences and recruiting histone acetyltransferases...
. It was recently renamed to Lysine Demethylase 5A (KDM5A).
Enzymatically can be designated as a trimethyllysine dioxygenase
Trimethyllysine dioxygenase
In enzymology, a trimethyllysine dioxygenase is an enzyme that catalyzes the chemical reactionThe 3 substrates of this enzyme are N6,N6,N6-trimethyl-L-lysine, 2-oxoglutarate, and O2, whereas its 3 products are 3-hydroxy-N6,N6,N6-trimethyl-L-lysine, succinate, and CO2.This enzyme belongs to the...
. (EC 1.14.11.8)
Interactions
JARID1A has been shown to interactProtein-protein interaction
Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...
with Estrogen receptor alpha
Estrogen receptor alpha
Estrogen receptor alpha , also known as NR3A1 , is a nuclear receptor that is activated by the sex hormone estrogen...
, LMO2
LMO2
LIM domain only 2 , also known as LMO2, is a protein which in humans is encoded by the LMO2 gene.- Function :LMO2 encodes a cysteine-rich, two LIM domain protein that is required for yolk sac erythropoiesis. The LMO2 protein has a central and crucial role in hematopoietic development and is highly...
and Retinoblastoma protein
Retinoblastoma protein
The retinoblastoma protein is a tumor suppressor protein that is dysfunctional in the majority types of cancer. One highly studied function of pRb is to prevent excessive cell growth by inhibiting cell cycle progression until a cell is ready to divide...
.
JARID1A is a major component of the circadian clock, the upregulation of which at the end of the sleep phase blocks HDAC1 activity. Blocking HDAC1 activity results in an upregulation of CLOCK and BMAL1 and consequent upregulation of PER proteins. The PSF (polypyrimidine tract-binding protein-associated splicing factor) within the PER complex recruits SIN3A, a scaffold for assembly of transcriptional inhibitory complexes and rhythmically delivers histone deacetylases to the Per1 promoter, which repress Per1 transcription.[PMID 21960634] [PMID 21680841]
Knockdown of JARID1A promoted osteogenic differentiation of human adipose-derived stromal cells in vitro and in vivo and resulted in marked increases of mRNA expression of osteogenesis-associated genes such as alkaline phosphatase (ALP), osteocalcin (OC), and osterix (OSX). RBP2 was shown to occupy the promoters of OSX and OC to maintain the level of the H3K4me3 mark by chromatin immunoprecipitation assays. RBP2 was also physically and functionally associated with RUNX2, an essential transcription factor that governed osteoblastic differentiation. RUNX2 knockdown impaired the repressive activity of RBP2 in osteogenic differentiation of human adipose-derived stromal cells. [PMID 21604327]