CR Name:
Species:    Tissue or Cell: 

Chromatin Regulator

Alias

ASH2LASH2;ASH2L1;ASH2L2;Bre2

External Links:

Wiki    GeneCards    NCBI    UniProt

Related histone modifications:

H3K4me1;H3K4me2;H3K4me3

Introduction

Full name: ASH2 Like Histone Lysine Methyltransferase Complex Subunit. Ash2l is a member of the Trx family and was identified in a screen for Drosophila mutants exhibiting imaginal disc abnormalities and late larval/early pupal lethality(1),is a component of the mixed lineage leukemia (MLL) family members 1-4,Setd1A,and Setd1B mammalian histone H3K4 methyltransferase complexes and is essential to maintain global trimethylation of histone H3K4(2). Ash2l is composed of a C4 zinc-finger motif located on its N-terminal region and an SPIa and ryanodine receptor (SPRY) domain located on its C-terminal region,the SPRY domain is required for binding to RbBP5 and N-terminal HWH(helix-wing-helix) domain is required for binding to DNA(3,4,5).

Function and Interaction

Ash2l is a trithorax protein,is one of the core components of mixed lineage leukemia (MLL) protein complexes which add methyl group to histone H3K4 and contribute to H3K4me1,me2,and me3 marks across the genome(6).The chromodomain of CHD1 can directly bind the H3K4me3 mark and forms a complex with Ash2l,suggesting that CHD1 function may depend on the H3K4me3 mark generated by the Ash2l-containing MLL complex(7).Ash2l is required for ES cell pluripotency and the global,active chromatin modifications associated with ES cells(8).Ash2l was recruited to the enhancer of the ERα gene through GATA3 to promote ERα transcription in breast cancers(9).

Disease Association

NA

ChIP-Seq data


SpeciesCell lineCell typeTissueDataDownloadSend to CistromeAnalysis FiguresComparisonReference
Mus musculusE14Embryonic Stem CellEmbryoGSE52071 ,GSM1258240
Click  DownloadClick24423662

ChIP-Seq data of related histone modifications


Products/SubstratesSpeciesCell lineCell typeTissueDataDownload Send to CistromeAnalysis FiguresReference
H3K4me1 Mus musculus None B Lymphocyte Spleen GSE51004 ,GSM1234488 Bed     Big wiggle
Click   Download25043028
H3K4me1 Mus musculus None B Lymphocyte Spleen GSE51004 ,GSM1234489 Bed     Big wiggle
Click   Download25043028
H3K4me3 Mus musculus None B Lymphocyte Spleen GSE51004 ,GSM1234517 Bed     Big wiggle
Click   Download25043028
H3K4me1 Mus musculus None B Lymphocyte Spleen GSE51004 ,GSM1234519 Bed     Big wiggle
Click   Download25043028
H3K4me3 Mus musculus E14 Embryonic Stem Cell Embryo GSE52071 ,GSM1258237 Bed     Big wiggle
Click   Download24423662
H3K4me3 Mus musculus E14 Embryonic Stem Cell Embryo GSE52071 ,GSM1276705 Bed     Big wiggle
Click   Download24423662
H3K4me2 Homo sapiens VCaP Epithelium Prostate GSE56086 ,GSM1354840 Bed     Big wiggle
Click   Download25552417
H3K4me3 Homo sapiens VCaP Epithelium Prostate GSE14092 ,GSM353603 Bed     Big wiggle
Click   Download20478527
H3K4me3 Homo sapiens VCaP Epithelium Prostate GSE14092 ,GSM353604 Bed     Big wiggle
Click   Download20478527
H3K4me3 Homo sapiens VCaP Epithelium Prostate GSE14092 ,GSM353620 Bed     Big wiggle
Click   Download20478527
H3K4me1 Homo sapiens VCaP Epithelium Prostate GSE14092 ,GSM353631 Bed     Big wiggle
Click   Download20478527
H3K4me2 Homo sapiens VCaP Epithelium Prostate GSE14092 ,GSM353632 Bed     Big wiggle
Click   Download20478527
H3K4me2 Mus musculus None B Lymphocyte Spleen GSE20852 ,GSM558118 Bed     Big wiggle
Click   Download20671152
H3K4me3 Mus musculus None B Lymphocyte Spleen GSE20852 ,GSM566955 Bed     Big wiggle
Click   Download20671152
H3K4me3 Mus musculus None B Lymphocyte Spleen GSE20852 ,GSM566975 Bed     Big wiggle
Click   Download20671152
H3K4me3 Mus musculus E14 Embryonic Stem Cell Embryo GSE26136 ,GSM651193 Bed     Big wiggle
Click   Download21335234
H3K4me2 Mus musculus None B Lymphocyte Spleen GSE35915 ,GSM877343 Bed     Big wiggle
Click   Download22431510
H3K4me2 Mus musculus E14 Embryonic Stem Cell Embryo GSE38596 ,GSM881353 Bed     Big wiggle
Click   Download22682255
H3K4me1 Mus musculus E14 Embryonic Stem Cell Embryo GSE38596 ,GSM881360 Bed     Big wiggle
Click   Download22682255
H3K4me2 Mus musculus E14 Embryonic Stem Cell Embryo GSE38596 ,GSM881361 Bed     Big wiggle
Click   Download22682255
H3K4me1 Mus musculus E14 Embryonic Stem Cell Embryo GSE38596 ,GSM881369 Bed     Big wiggle
Click   Download22682255
H3K4me2 Mus musculus E14 Embryonic Stem Cell Embryo GSE38596 ,GSM881370 Bed     Big wiggle
Click   Download22682255

Notice: For bigwiggle or bed file download, if the browser cannot automatically download the file, users can right click the hyperlink and then click the "Save link as..." button, which will automatically redirect to download dialogue box, or click the "Copy link address" button and access the website in a new tab page. For data analysis in Cistrome, users should first login into the Cistrome website, then press the "Send Bed" or "Send Big wiggle" button. For data download by Cistrome, users can follow this tutorial.

References

1.Shearn, A., Rice, T., Garen, A., and Gehring, W. (1971). Imaginal disc abnormalities in lethal mutants of Drosophila. Proc Natl Acad Sci U S A 68, 2594-2598.
2.Butler, J.S., Zurita-Lopez, C.I., Clarke, S.G., Bedford, M.T., and Dent, S.Y. (2011). Protein-arginine methyltransferase 1 (PRMT1) methylates Ash2L, a shared component of mammalian histone H3K4 methyltransferase complexes. J Biol Chem 286, 12234-12244.
3.Sarvan, S., Avdic, V., Tremblay, V., Chaturvedi, C.P., Zhang, P., Lanouette, S., Blais, A., Brunzelle, J.S., Brand, M., and Couture, J.F. (2011). Crystal structure of the trithorax group protein ASH2L reveals a forkhead-like DNA binding domain. Nat Struct Mol Biol 18, 857-859.
4.Cao, F., Chen, Y., Cierpicki, T., Liu, Y., Basrur, V., Lei, M., and Dou, Y. (2010). An Ash2L/RbBP5 heterodimer stimulates the MLL1 methyltransferase activity through coordinated substrate interactions with the MLL1 SET domain. PLoS One 5, e14102.
5.Avdic, V., Zhang, P., Lanouette, S., Groulx, A., Tremblay, V., Brunzelle, J., and Couture, J.F. (2011). Structural and biochemical insights into MLL1 core complex assembly. Structure 19, 101-108.
6.Malik, S., and Bhaumik, S.R. (2010). Mixed lineage leukemia: histone H3 lysine 4 methyltransferases from yeast to human. FEBS J 277, 1805-1821.
7.Sims, R.J., 3rd, Millhouse, S., Chen, C.F., Lewis, B.A., Erdjument-Bromage, H., Tempst, P., Manley, J.L., and Reinberg, D. (2007). Recognition of trimethylated histone H3 lysine 4 facilitates the recruitment of transcription postinitiation factors and pre-mRNA splicing. Mol Cell 28, 665-676.
8.Wan, M., Liang, J., Xiong, Y., Shi, F., Zhang, Y., Lu, W., He, Q., Yang, D., Chen, R., Liu, D., Barton, M., Songyang, Z. (2013). The trithorax group protein ash2l is essential for pluripotency and maintaining open chromatin in embryonic stem cells. Journal of Biological Chemistry, 288(7), 5039-48.
9.Qi, J., Huo, L., Zhu, Y.T., and Zhu, Y.J. (2014). Absent, small or homeotic 2-like protein (ASH2L) enhances the transcription of the estrogen receptor alpha gene through GATA-binding protein 3 (GATA3). J Biol Chem 289, 31373-31381.

Figure Gallery

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About Chromatin Regulator

Chromatin Regulator Cistrome
is a unique database integrating curated information of CRs, CR ChIP-seq datasets, CR related HM ChIP-seq datasets, and analysis of the relationship between CRs and HMs ChIP-seq pairs in human and mouse.

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