BACH2 immunodeficiency illustrates an association between super-enhancers and haploinsufficiency

• Published in: Nature immunology Vol. 18; no. 7; pp. 813 - 823
• Main Authors: Afzali, Behdad, Grönholm, Juha, Vandrovcova, Jana, O'Brien, Charlotte, Sun, Hong-Wei, Vanderleyden, Ine, Davis, Fred P, Khoder, Ahmad, Zhang, Yu, Hegazy, Ahmed N, Villarino, Alejandro V, Palmer, Ira W, Kaufman, Joshua, Watts, Norman R, Kazemian, Majid, Kamenyeva, Olena, Keith, Julia, Sayed, Anwar, Kasperaviciute, Dalia, Mueller, Michael, Hughes, Jason D, Fuss, Ivan J, Sadiyah, Mohammed F, Montgomery-Recht, Kim, McElwee, Joshua, Restifo, Nicholas P, Strober, Warren, Linterman, Michelle A, Wingfield, Paul T, Uhlig, Holm H, Roychoudhuri, Rahul, Aitman, Timothy J, Kelleher, Peter, Lenardo, Michael J, O'Shea, John J, Cooper, Nichola, Laurence, Arian D J
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.07.2017; Nature Publishing Group
• Subjects: 13/106; 13/109; 13/51; 13/89; 14/19; 631/250/248; 631/250/249/2512; 64/110; 82/80; Adrenal Cortex Hormones - therapeutic use; Adult; Autoimmune diseases; Autoimmune Diseases - complications; Autoimmune Diseases - genetics; Basic-Leucine Zipper Transcription Factors - genetics; Biomedicine; Colitis - complications; Colitis - genetics; Colitis - pathology; Enhancers; Female; Fever - complications; Fever - drug therapy; Fever - genetics; Genomes; Haploinsufficiency; Heterozygote; Humans; Immunodeficiency; Immunologic Deficiency Syndromes - complications; Immunologic Deficiency Syndromes - genetics; Immunology; Infectious Diseases; Intestine; Lymphocytes; Lymphocytes B; Lymphocytes T; Lymphopenia - complications; Lymphopenia - genetics; Male; Middle Aged; Mutation; Pancytopenia - complications; Pancytopenia - drug therapy; Pancytopenia - genetics; Pedigree; Polymorphism, Single Nucleotide; Primary immunodeficiencies; Recurrence; Respiratory Tract Infections - complications; Respiratory Tract Infections - diagnostic imaging; Respiratory Tract Infections - genetics; Rodents; Splenomegaly - complications; Splenomegaly - genetics; Syndrome; Tomography, X-Ray Computed; Transcription factors; Young Adult
• ISSN: 1529-2908; 1529-2916; 1529-2916
• DOI: 10.1038/ni.3753

BACH2 is required for lymphocyte differentiation. Afzali et al . describe mutations that cause BACH2 disruption, immunodeficiency and autoinflammatory disease via haploinsufficiency, a mechanism shared by other super-enhancer-regulated genes. The transcriptional programs that guide lymphocyte differ...