Source:
Generated By: https://synbiohub.org/public/igem/igem2sbol/1
Created by: Emilie Gounin
Date created: 2016-10-13 11:00:00
Date modified: 2016-10-14 09:43:35
DNMT3a/DNMT3l
| Types | DnaRegion |
| Roles | polypeptide_domain Protein_Domain |
| Sequences | BBa_K1935019_sequence (Version 1) |
Description
Dnmt3a: Required for genome-wide de novo methylation and is essential for the establishment of DNA methylation patterns during development. DNA methylation is coordinated with methylation of histones. It modifies DNA in a non-processive manner and also methylates non-CpG sites. May preferentially methylate DNA linker between 2 nucleosomal cores and is inhibited by histone H1. Plays a role in paternal and maternal imprinting. Required for methylation of most imprinted loci in germ cells. Acts as a transcriptional corepressor for ZBTB18. Recruited to trimethylated 'Lys-36' of histone H3 (H3K36me3) sites. Can actively repress transcription through the recruitment of HDAC activity.Dnmt3l: Catalytically inactive regulatory factor of DNA methyltransferases. It is essential for the function of DNMT3A and DNMT3B. Activates DNMT3A and DNMT3B by binding to their catalytic domain. Accelerates the binding of DNA and AdoMet to the methyltransferases and dissociates from the complex after DNA binding to the methyltransferases. Recognizes unmethylated histone H3 lysine 4 (H3K4) and induces de novo DNA methylation by recruitment or activation of DNMT3.
In vertebrates, Transcription Start Sites (TSS) are divided into two categories:
On the one hand, there are specific consensus sequences, such as the TATA box for example, that are recognized by transcription factors that recruit in turn RNA polymerases.
On the other hand, there are about 1 kb large DNA sequences with a high content of cytosine and guanine dinucleotides.
This last group is named ???CpG promoters??? or ???CGIs??? (CpG islands). It is the one which is targeted by DNA methyltransferases. Indeed, these regions are typically non-methylated, compared to the rest of the genome.
In addition to their CG abundance, CGIs show a particular histone modification signature: they are enriched in H3K4me3.This characteristic has consequences: it maintains DNMTs inactive. Indeed, DNA methyltransferases get activated only when bound to H3K27me3 via their ADD domain. That may explain why CGI are most of the time unmethylated.
Notes
in progressSource
Dnmt3a http://www.uniprot.org/uniprot/Q9Y6K1Dnmt3l http://www.uniprot.org/uniprot/Q9UJW3