The RAG-2 Inhibitory Domain Gates Accessibility of the V(D)J Recombinase to Chromatin

Molecular and Cellular Biology
Alyssa WardS Desiderio

Abstract

Accessibility of antigen receptor loci to RAG is correlated with the presence of H3K4me3, which binds to a plant homeodomain (PHD) in the RAG-2 subunit and promotes V(D)J recombination. A point mutation in the PHD, W453A, eliminates binding of H3K4me3 and impairs recombination. The debilitating effect of the W453A mutation is ameliorated by second-site mutations that locate an inhibitory domain in the interval from residues 352 through 405 of RAG-2. Disruption of the inhibitory domain stimulates V(D)J recombination within extrachromosomal substrates and at endogenous antigen receptor loci. Association of RAG-1 and RAG-2 with chromatin at the IgH locus in B cell progenitors is dependent on recognition of H3K4me3 by the PHD. Strikingly, disruption of the inhibitory domain permits association of RAG with the IgH locus in the absence of H3K4me3 binding. Thus, the inhibitory domain acts as a gate that prohibits RAG from accessing the IgH locus unless RAG-2 is engaged by H3K4me3.

References

Apr 1, 1991·Molecular and Cellular Biology·A Alessandrini, S V Desiderio
May 25, 1994·Nucleic Acids Research·M J SadofskyM Gellert
May 25, 1994·Nucleic Acids Research·C A Cuomo, M A Oettinger
Mar 19, 1999·Molecular and Cellular Biology·S B SteenD B Roth
Jun 5, 2002·Annual Review of Biochemistry·Martin Gellert
Sep 23, 2003·Proceedings of the National Academy of Sciences of the United States of America·Katrina B MorsheadMarjorie A Oettinger
Feb 27, 2004·Nature Immunology·Oleg OsipovichEugene M Oltz
Aug 26, 2004·Nucleic Acids Research·Sadiqur R TalukderYoshiko Akamatsu
Dec 28, 2004·Nature Immunology·Maya GoldmitYehudit Bergman
Mar 23, 2006·Annual Review of Immunology·David JungFrederick W Alt
May 29, 2007·Molecular and Cellular Biology·Daniel J BollandAnne E Corcoran
Nov 21, 2007·Proceedings of the National Academy of Sciences of the United States of America·Santiago Ramón-MaiquesWei Yang
Nov 23, 2007·Nature·Adam G W MatthewsMarjorie A Oettinger
Dec 15, 2010·Proceedings of the National Academy of Sciences of the United States of America·Gabrielle J GrundyMartin Gellert
Jul 12, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Eric J GapudBarry P Sleckman
Jan 31, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Miyo Aoki-OtaDavid Nemazee
Sep 21, 2013·Annual Review of Genetics·Ludovic Deriano, David B Roth
Mar 13, 2014·DNA Repair·Nicholas R PannunzioMichael R Lieber
Feb 25, 2015·Nature·Min-Sung KimMartin Gellert
Feb 9, 2017·Proceedings of the National Academy of Sciences of the United States of America·John BettridgeStephen Desiderio

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.