Chromatin Regulator Cistrome

Chromatin Regulator

Alias

RAG2

RAG-2

External Links:

Wiki GeneCards NCBI UniProt

Related histone modifications:

H3K4me3

Introduction

Full Name: Recombination-activating gene 2 . RAG2 is a recombination-activating gene that binds to trimethylated lysine 4 on histone 3 (H3K4me3) through its plant homeodomain (PHD) finger. Rather than exhibiting detectable DNA binding activity by itself, RAG2 can interact with RAG1, thereby forming the RAG1/RAG2 synaptic complex, increasing the specificity and affinity of RSS (recombination signal sequence) binding. the expression of RAG2 can be regulated by E2A, FOXO1 and FOXP1 in cancer cells. This chain of events is essential for DNA cleavage and maintaining genomic stability as well as inhibiting the pathogenesis of lymphoid malignancies (1-11).

Function and Interaction

RAG2, together with RAG1, is thought to be required for the initiation of V(D)J (V (variable), D (diversity), and J (joining)) recombination, which is a site-specific recombination reaction that facilitates the assembly of antigen receptor genes (3,7).

Disease Association

Mutations in RAG2 are found in SCID (severe combined immunodeficiency) and Omenn syndrome (8-9).

ChIP-Seq data

Species	Cell line	Cell type	Tissue	Data	Download	Send to Cistrome	Analysis Figures	Comparison	Reference
Mus musculus	None	Thymocyte	None	GSE69475 ,GSM1701794		Click Download	Click	26234156

ChIP-Seq data of related histone modifications

Products/Substrates	Species	Cell line	Cell type	Tissue	Data	Download	Analysis Figures	Reference
H3K4me3	Mus musculus	None	Thymocyte	None	GSE48817 ,GSM1185223	Bed Big wiggle	Click Download	23918392
H3K4me3	Mus musculus	NA	Pro-B Lymphocyte	NA	GSE53595 ,GSM1296576	Bed Big wiggle	Click Download	24509509
H3K4me3	Mus musculus	NA	Pro-B Lymphocyte	NA	GSE53595 ,GSM1296577	Bed Big wiggle	Click Download	24509509
H3K4me3	Mus musculus	NA	Pro-B Lymphocyte	NA	GSE53595 ,GSM1296579	Bed Big wiggle	Click Download	24509509
H3K4me3	Mus musculus	None	B Lymphocyte	None	GSE60005 ,GSM1463440	Bed Big wiggle	Click Download	26477271
H3K4me3	Mus musculus	None	B Lymphocyte	None	GSE69475 ,GSM1701802	Bed Big wiggle	Click Download	26234156
H3K4me3	Homo sapiens	None	Thymocyte	None	GSE69475 ,GSM1701808	Bed Big wiggle	Click Download	26234156
H3K4me3	Homo sapiens	None	Thymocyte	None	GSE69475 ,GSM1701809	Bed Big wiggle	Click Download	26234156
H3K4me3	Mus musculus	None	B Lymphocyte	None	GSE71698 ,GSM1843355	Bed Big wiggle	Click Download	26779602
H3K4me3	Mus musculus	NA	Thymocyte	Thymus	GSE21207 ,GSM530317	Bed Big wiggle	Click Download	20398922
H3K4me3	Mus musculus	NA	Thymocyte	Thymus	GSE32311 ,GSM803112	Bed Big wiggle	Click Download	22080921
H3K4me3	Mus musculus	NA	Thymocyte	Thymus	GSE32311 ,GSM803122	Bed Big wiggle	Click Download	22080921

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. Matthews, A.G.W., Kuo, A.J., Ramon-Maiques, S., Han, S.M., Champagne, K.S., Ivanov, D., Gallardo, M., Carney, D., Cheung, P., Ciccone, D.N. et al. (2007) RAG2 PHD finger couples histone H3 lysine 4 trimethylation with V(D)J recombination. Nature, 450, 1106-U1118.
2. Liu, Y., Subrahmanyam, R., Chakraborty, T., Sen, R. and Desiderio, S. (2007) A plant homeodomain in Rag-2 that binds hypermethylated lysine 4 of histone H3 is necessary for efficient antigen-receptor-gene rearrangement. Immunity, 27, 561-571.
3. Ji, Y.H., Resch, W., Corbett, E., Yamane, A., Casellas, R. and Schatz, D.G. (2010) The In Vivo Pattern of Binding of RAG1 and RAG2 to Antigen Receptor Loci (vol 141, pg 419, 2010). Cell, 143, 170-170.
4. Shimazaki, N., Tsai, A.G. and Lieber, M.R. (2009) H3K4me3 Stimulates the V(D)J RAG Complex for Both Nicking and Hairpinning in trans in Addition to Tethering in cis: Implications for Translocations. Mol Cell, 34, 535-544.
5. Callebaut, I. and Mornon, J.P. (1998) The V(D)J recombination activating protein RAG2 consists of a six-bladed propeller and a PHD fingerlike domain, as revealed by sequence analysis. Cell Mol Life Sci, 54, 880-891.
6. Elkin, S.K., Ivanov, D., Ewalt, M., Ferguson, C.G., Hyberts, S.G., Sun, Z.Y.J., Prestwich, G.D., Yuan, J.Y., Wagner, G., Oettinger, M.A. et al. (2005) A PHD finger motif in the C terminus of RAG2 modulates recombination activity. J Biol Chem, 280, 28701-28710.
7. Swanson, P.C. (2004) The bounty of RAGs: recombination signal complexes and reaction outcomes. Immunol Rev, 200, 90-114.
8. Dalal, I., Tasher, D., Somech, R., Etzioni, A., Garti, B.Z., Lev, D., Cohen, S., Somekh, E. and Leshinsky-Silver, E. (2011) Novel mutations in RAG1/2 and ADA genes in Israeli patients presenting with T-B- SCID or Omenn syndrome. Clinical Immunology, 140, 284-290.
9. Safaei, S., Pourpak, Z., Moin, M. and Houshmand, M. (2011) IL7R and RAG1/2 genes mutations/polymorphisms in patients with SCID. Iran J Allergy Asthma Immunol, 10, 129-132.
10. Deriano, L., Chaumeil, J., Coussens, M., Multani, A., Chou, Y., Alekseyenko, A.V., Chang, S., Skok, J.A. and Roth, D.B. (2011) The RAG2 C terminus suppresses genomic instability and lymphomagenesis. Nature, 471, 119-123.
11. Chen, Z., Xiao, Y., Zhang, J., Li, J., Liu, Y., Zhao, Y., Ma, C., Luo, J., Qiu, Y., Huang, G. et al. (2011) Transcription factors E2A, FOXO1 and FOXP1 regulate recombination activating gene expression in cancer cells. PLoS One, 6, e20475.

Chromatin Regulator Cistrome
A knowledgebase for chromatin modifying enzymes and chromatin remodelers