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PALB2 associates with active genes through its major binding partner, MRG15, which recognizes histone H3 trimethylated at lysine 36 (H3K36me3) by the SETD2 methyltransferase
Both MRG15 CD and Pf1 PHD1 (zeige EGLN2 Proteine) bind to their targets with >100 muM affinity.
While the present study expands on the role of MRG15 in the control of genomic stability, weak associations can not be ruled out for potential low-penetrance variants at MORF4L1 and breast cancer risk among BRCA2 (zeige BRCA2 Proteine) mutation carriers
it seems unlikely that any constitutional changes in MRG15 confer an increased risk for breast cancer.
Site-directed mutagenesis studies of a prototypic MRG (zeige FABP7 Proteine) domain from human MRG15 based on the X-ray structure and bioinformatics identify key residues involved in the binding of PAM14 (zeige MRFAP1 Proteine) and MRGBP (zeige MRGBP Proteine).
identify MRG15 residues that form a shallow hydrophobic pocket to interact with the N-terminal 50 residues of PAM14 (zeige MRFAP1 Proteine) through primarily hydrophobic interactions
The MRG15 chromo domain may function as an adaptor module which can bind to a modified histone H3 (zeige HIST3H3 Proteine) in a mode different from that of the HP1 (zeige DEFA1 Proteine)/Pc chromo domains.
MORF4 has a role in cellular aging, and MRG15 associates with both histone deacetylases and histone acetyl transferase (zeige HAT1 Proteine) complexes [review]
RBP2 (zeige KDM5A Proteine) associates with MRG15 complex to maintain reduced H3K4 methylation at transcribed regions, which may ensure the transcriptional elongation state
MRG15 is a novel PALB2 (zeige PALB2 Proteine)-interacting factor involved in homologous recombination
In round spermatids, MRG15 colocalizes with splicing factors PTBP1 (zeige PTBP1 Proteine) and PTBP2 (zeige PTBP2 Proteine) at H3K36me3 sites between the exons and single intron of transition nuclear protein 2 (Tnp2 (zeige TNP2 Proteine)). Thus, our results reveal that MRG15 is essential for pre-mRNA splicing during spermatogenesis and that epigenetic regulation of pre-mRNA splicing by histone modification could be useful to understand not only spermatogenesis but also, epigenetic disorder
HDAC2 (zeige HDAC2 Proteine)-dependent deacetylation of MORF4L1 enhances MORF4L1 homodimerization, thus facilitating the functionality of complex formation to repress cell proliferation.
DNA damage foci, as indicated by immunostaining for gammaH2AX (zeige H2AFX Proteine) and 53BP1 (zeige TP53BP1 Proteine), are detectable in a sub-population of Mrg15 deficient NSC cultures under normal growing conditions and the majority of p21-positive cells are also positive for 53BP1 (zeige TP53BP1 Proteine) foci.
MRG15 has an essential role in embryonic development via chromatin remodeling and transcriptional regulation.
Formation of phosphorylated H2AX (zeige H2AFX Proteine) and 53BP1 (zeige TP53BP1 Proteine) foci was delayed in Mrg15 mutant versus wild-type cells following irradiation. These data implicate a novel role for MRG15 in DNA-damage repair in mammalian cells.
Our results demonstrate that MRG15 has more than one function in neurogenesis and defines a novel role for this chromatin regulator that integrates proliferation and cell-fate determination in neurogenesis during development.
Ash1 (zeige ASCL1 Proteine) HMTase activity is activated by MRG15, a subunit of the identified Ash1 (zeige ASCL1 Proteine) complex, and that this complex, rather than the Ash1 (zeige ASCL1 Proteine) protein alone, is the active form of this H3K36 methyltransferase, both in vitro and in vivo.
Mrg15 interacts with Cap-H2 condensin subunit.
Drosophila DmMRG15 gene function is required for female fertility, larval survival and adult life span, and provides reagents that should be useful for further dissecting the role of DmMRG15 in cell proliferation and aging.
Component of the NuA4 histone acetyltransferase complex which is involved in transcriptional activation of select genes principally 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. This complex may be required for the activation of transcriptional programs associated with oncogene and proto-oncogene mediated growth induction, tumor suppressor mediated growth arrest and replicative senescence, apoptosis, and DNA repair. The NuA4 complex ATPase and helicase activities seem to be, at least in part, contributed by the association of RUVBL1 and RUVBL2 with EP400. NuA4 may also play a direct role in DNA repair when directly recruited to sites of DNA damage. Also component of the mSin3A complex which acts to repress transcription by deacetylation of nucleosomal histones. Required for homologous recombination repair (HRR) and resistance to mitomycin C (MMC). Involved in the localization of PALB2, BRCA2 and RAD51, but not BRCA1, to DNA-damage foci (By similarity).
Esa1p-associated factor 3 homolog
, MORF-related gene 15 protein
, MORF-related gene on chromosome 15
, mortality factor 4-like protein 1
, protein MSL3-1
, transcription factor-like protein MRG15
, testis expressed gene 189
, testis-expressed gene 189 protein
, MORF-related gene 15
, mortality factor 4 like 2