Male-specific lethal 3 homolog (MSL3) is a component of the MSL complex []. MSL3 has a chromodomain by which it interacts with DNA [, ]and an MRG domain with which it interacts with MSL1 [].The male-specific lethal (MSL) complex is a histone acetyltransferase with specificity for histone H4 'lysine-16' in chromatin. The complex consists of MOF, MSL1, MSL2, and MSL3 []. The complex was first identified in Drosophila.
E3 ubiquitin-protein ligase MSL2 (MSL2; [intenz:6.3.2.-]) is an E3 ubiquitin ligase that promotes monoubiquitination of histone H2B at 'Lys-35' (H2BK34Ub), but not that of H2A. It is a component of MSL complex [].The male-specific lethal (MSL) complex is a histone acetyltransferase with specificity for histone H4 'lysine-16' in chromatin. The complex consists of MOF, MSL1, MSL2, and MSL3 []. The complex was first identified in Drosophila.
Histone acetyltransferase KAT8 () has activity directed towards histones H3, H2A and H4 []and is the active component of the MSL and NSL complexes []. KAT8 autoacetylates itself on Lys-274 which is a requirement for binding to histone H4 []. In Drosophila melanogaster this protein is known as 'males-absent on the first protein' (MOF) [].The male-specific lethal (MSL) complex is a histone acetyltransferase with specificity for histone H4 'lysine-16' in chromatin. The complex consists of MOF, MSL1, MSL2, and MSL3 []. The complex was first identified in Drosophila.
This entry represents MRG protein family, whose members include MORF4L1/2 (MRG15/MRGX) and MSL3L1/2 from humans, ESA1-associated factor 3 (Eaf3) from yeasts and male-specific lethal 3 (MSL3) from flies. They contain an N-terminal chromodomain that binds H3K36me3, a histone mark associated with transcription elongation []. Saccharomyces cerevisiae Eaf3 is a component of both NuA4 histone acetyltransferase and Rpd3S histone deacetylase complexes [, ]. It was found that Eaf3 mediates preferential deacetylation of coding regions through an interaction between the Eaf3 chromodomain and methylated H3-K36 that presumably results in preferential association of the Rpd3 complex []. The Drosophila MSL proteins (MSL1, MSL2, MSL3, MLE, and MOF) are essential for elevating transcription of the single X chromosome in the male (X chromosome dosage compensation) []. Together with two partlyredundant non-coding RNAs, roX1 and roX2, they form the MSL complex, also known as dosage compensation complex or DCC. MSL complex upregulates transcription by spreading the histone H4 Lys16 (H4K16) acetyl mark []and allows compensation for the loss of one X-chromosomal allele by increasing the transcription from the retained allele []. The MSL3 chromodomain has been shown to bind DNA and methylated H4K20 in vitro []. Human MORF4L1, also known as MRG15, is a component of the NuA4 histone acetyltransferase complex that transcriptional activates genes by acetylation of nucleosomal histones H4 and H2A. This modification may both alter nucleosome - DNA interactions and promote interaction of the modified histones with other proteins which positively regulate transcription. NuA4 complex may also play a direct role in DNA repair when directly recruited to sites of DNA damage. MRG15 is also a component of the mSin3A/Pf1/HDAC complex which acts to repress transcription by deacetylation of nucleosomal histones. MRG15 was found to interact with PALB2, a tumour suppressor protein that plays a crucial role in DNA damage repair by homologous recombination []. Furthermore, MRG15 play a role in the response to double strand breaks (DSBs) by recruiting the BRCA complex (BRCA1, PALB2, BRCA2 and RAD51) to sites of damaged DNA [, ].
The CHROMO (CHRromatin Organization MOdifier) domain [, , , ]is a conserved region of around 60 amino acids, originally identified in Drosophila modifiers of variegation. These are proteins that alter the structure of chromatin to the condensed morphology of heterochromatin, a cytologically visible condition where gene expression is repressed. In one of these proteins, Polycomb, the chromo domain has been shown to be important for chromatin targeting. Proteins that contain a chromo domain appear to fall into 3 classes. The first class includes proteins having an N-terminal chromo domain followed by a region termed the chromo shadow domain, with weak but significant sequence similarity to the N-terminal chromo domain [], eg. Drosophila and human heterochromatin protein Su(var)205 (HP1). The second class includes proteins with a single chromo domain, eg. Drosophila protein Polycomb (Pc); mammalian modifier 3; human Mi-2 autoantigen and several yeast and Caenorhabditis elegans hypothetical proteins. In the third class paired tandem chromo domains are found, eg. in mammalian DNA-binding/helicase proteins CHD-1 to CHD-4 and yeast protein CHD1.Functional dissections of chromo domain proteins suggests a mechanistic role for chromo domains in targeting chromo domain proteins to specific regions of the nucleus. The mechanism of targeting may involve protein-protein and/or protein/nucleic acid interactions. Hence, several line of evidence show that the HP1 chromo domain is a methyl-specific histone binding module, whereas the chromo domain of two protein components of the drosophila dosage compensation complex, MSL3 and MOF, contain chromo domains that bind to RNA in vitro [].The high resolution structures of HP1-family protein chromo and chromo shadow domain reveal a conserved chromo domain fold motif consisting of three β-strands packed against an α-helix. The chromo domain fold belongs to the OB (oligonucleotide/oligosaccharide binding)-fold class found in a variety of prokaryotic and eukaryotic nucleic acid binding protein [].
The CHROMO (CHRromatin Organization MOdifier) domain [, , , ]is a conserved region of around 60 amino acids, originally identified in Drosophila modifiers of variegation. These are proteins that alter the structure of chromatin to the condensed morphology of heterochromatin, a cytologically visible condition where gene expression is repressed. In one of these proteins, Polycomb, the chromo domain has been shown to be important for chromatin targeting. Proteins that contain a chromo domain appear to fall into 3 classes. The first class includes proteins having an N-terminal chromo domain followed by a region termed the chromo shadow domain, with weak but significant sequence similarity to the N-terminal chromo domain [], eg. Drosophila and human heterochromatin protein Su(var)205 (HP1). The second class includes proteins with a single chromo domain, eg. Drosophila protein Polycomb (Pc); mammalian modifier 3; human Mi-2 autoantigen and several yeast and Caenorhabditis elegans hypothetical proteins. In the third class paired tandem chromo domains are found, eg. in mammalian DNA-binding/helicase proteins CHD-1 to CHD-4 and yeast protein CHD1.Functional dissections of chromo domain proteins suggests a mechanistic role for chromo domains in targeting chromo domain proteins to specific regions of the nucleus. The mechanism of targeting may involve protein-protein and/or protein/nucleic acid interactions. Hence, several line of evidence show that the HP1 chromo domain is a methyl-specific histone binding module, whereas the chromo domain of two protein components of the drosophila dosage compensation complex, MSL3 and MOF, contain chromo domains that bind to RNA in vitro [].The high resolution structures of HP1-family protein chromo and chromo shadow domain reveal a conserved chromo domain fold motif consisting of three β-strands packed against an α-helix. The chromo domain fold belongs to the OB (oligonucleotide/oligosaccharide binding)-fold class found in a variety of prokaryotic and eukaryotic nucleic acid binding protein [].
The CHROMO (CHRromatin Organization MOdifier) domain [, , , ]is a conserved region of around 60 amino acids, originally identified in Drosophila modifiers of variegation. These are proteins that alter the structure of chromatin to the condensed morphology of heterochromatin, a cytologically visible condition where gene expression is repressed. In one of these proteins, Polycomb, the chromo domain has been shown to be important for chromatin targeting. Proteins that contain a chromo domain appear to fall into 3 classes. The first class includes proteins having an N-terminal chromo domain followed by a region termed the chromo shadow domain, with weak but significant sequence similarity to the N-terminal chromo domain [], eg. Drosophila and human heterochromatin protein Su(var)205 (HP1). The second class includes proteins with a single chromo domain, eg. Drosophila protein Polycomb (Pc); mammalian modifier 3; human Mi-2 autoantigen and several yeast and Caenorhabditis elegans hypothetical proteins. In the third class paired tandem chromo domains are found, eg. in mammalian DNA-binding/helicase proteins CHD-1 to CHD-4 and yeast protein CHD1.Functional dissections of chromo domain proteins suggests a mechanistic role for chromo domains in targeting chromo domain proteins to specific regions of the nucleus. The mechanism of targeting may involve protein-protein and/or protein/nucleic acid interactions. Hence, several line of evidence show that the HP1 chromo domain is a methyl-specific histone binding module, whereas the chromo domain of two protein components of the drosophila dosage compensation complex, MSL3 and MOF, contain chromo domains that bind to RNA in vitro [].The high resolution structures of HP1-family protein chromo and chromo shadow domain reveal a conserved chromo domain fold motif consisting of three β-strands packed against an α-helix. The chromo domain fold belongs to the OB (oligonucleotide/oligosaccharide binding)-fold class found in a variety of prokaryotic and eukaryotic nucleic acid binding protein [].This entry represents a conserved site in the chromo domain.
