InterPro domain: IPR008676

Saccharomyces cerevisiae Eaf3 is a component of both NuA4 histone acetyltransferase and Rpd3S histone deacetylase complexes [ 1 , 2 ]. 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 [ 3 ].

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 [ 4 ]. 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 [ 5 , 6 ].

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 [ 7 ].

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) [ 8 ]. 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 [ 9 ] and allows compensation for the loss of one X-chromosomal allele by increasing the transcription from the retained allele [ 10 ]. The MSL3 chromodomain has been shown to bind DNA and methylated H4K20 in vitro [ 11 ].

1. Alp13, an MRG family protein, is a component of fission yeast Clr6 histone deacetylase required for genomic integrity. EMBO J. 22, 2776-87
2. Role of endogenous dopamine on renal sodium excretion. Semin. Nephrol. 9, 91-3
3. Eaf3 chromodomain interaction with methylated H3-K36 links histone deacetylation to Pol II elongation. Mol. Cell 20, 971-8
4. Emerging role of the MORF/MRG gene family in various biological processes, including aging. Ann. N. Y. Acad. Sci. 1197, 134-41
5. Structural and functional conservation of the NuA4 histone acetyltransferase complex from yeast to humans. Mol. Cell. Biol. 24, 1884-96
6. MRG15 binds directly to PALB2 and stimulates homology-directed repair of chromosomal breaks. J. Cell. Sci. 123, 1124-30
7. Structural biology of the chromodomain: form and function. Gene 496, 69-78
8. The MOF chromobarrel domain controls genome-wide H4K16 acetylation and spreading of the MSL complex. Dev. Cell 22, 610-24
9. Corecognition of DNA and a methylated histone tail by the MSL3 chromodomain. Nat. Struct. Mol. Biol. 17, 1027-9
10. Dosage compensation: the beginning and end of generalization. Nat. Rev. Genet. 8, 47-57