12 results found
Bond J, Domaschenz R, Roman-Trufero M, et al., 2016, Direct interaction of Ikaros and Foxp1 modulates expression of the G protein-coupled receptor G2A in B-lymphocytes and acute lymphoblastic leukemia, Oncotarget, Vol: 7, Pages: 65923-65936, ISSN: 1949-2553
Ikaros and Foxp1 are transcription factors that play key roles in normal lymphopoiesis and lymphoid malignancies. We describe a novel physical and functional interaction between the proteins, which requires the central zinc finger domain of Ikaros. The Ikaros-Foxp1 interaction is abolished by deletion of this region, which corresponds to the IK6 isoform that is commonly associated with high-risk acute lymphoblastic leukemia (ALL). We also identify the Gpr132 gene, which encodes the orphan G protein-coupled receptor G2A, as a novel target for Foxp1. Increased expression of Foxp1 enhanced Gpr132 transcription and caused cell cycle changes, including G2 arrest. Co-expression of wild-type Ikaros, but not IK6, displaced Foxp1 binding from the Gpr132 gene, reversed the increase in Gpr132 expression and inhibited G2 arrest. Analysis of primary ALL samples revealed a significant increase in GPR132 expression in IKZF1-deleted BCR-ABL negative patients, suggesting that levels of wild-type Ikaros may influence the regulation of G2A in B-ALL. Our results reveal a novel effect of Ikaros haploinsufficiency on Foxp1 functioning, and identify G2A as a potential modulator of the cell cycle in Ikaros-deleted B-ALL.
Sabbattini P, Sjoberg M, Nikic S, et al., 2014, An H3K9/S10 methyl-phospho switch modulates Polycomb and Pol II binding at repressed genes during differentiation, MOLECULAR BIOLOGY OF THE CELL, Vol: 25, Pages: 904-915, ISSN: 1059-1524
Auner HW, Beham-Schmid C, Dillon N, et al., 2010, The life span of short-lived plasma cells is partly determined by a block on activation of apoptotic caspases acting in combination with endoplasmic reticulum stress, BLOOD, Vol: 116, Pages: 3445-3455, ISSN: 0006-4971
Sabbattini P, Canzonetta C, Sjoberg M, et al., 2007, Novel role for the Aurora B kinase in epigenetic marking of silent chromatin in differentiated postmitotic cells, EMBO JOURNAL, Vol: 26, Pages: 4657-4669, ISSN: 0261-4189
Thompson EC, Cobb BS, Sabbattini P, et al., 2007, Ikaros DNA-binding proteins as integral components of B cell developmental-stage-specific regulatory circuits., Immunity, Vol: 26, Pages: 335-344, ISSN: 1074-7613
Ikaros DNA-binding proteins are critical for the development of lymphocytes and other hematopoietic lineages, but it remains unclear how they cooperate with other regulators of signaling and transcription to achieve ordered gene expression during development. Here, we show that Ikaros proteins regulate the pre-BCR component lambda5 in a stage-specific manner. In pre-BI cells, Ikaros modulated lambda5 expression in competition with the transcriptional activator EBF. This required Ikaros binding to the Igll1 (lambda5) promoter and was abolished either by mutation of the Ikaros DNA-binding domain or by deletion of a single Ikaros site from the Igll1 promoter. At the transition from the pre-BI to pre-BII stage, the expression of the Ikaros family member Aiolos was upregulated and required for the efficient silencing of Igll1. Aiolos expression was controlled by pre-BCR signals via the adaptor protein SLP-65. Thus, pre-BCR signaling regulates Aiolos and the silencing of Igll1 via a developmental-stage-specific feedback loop.
Minaee S, Farmer D, Georgiou A, et al., 2005, Mapping and functional analysis of regulatory sequences in the mouse lambda 5-VpreB1 domain, MOLECULAR IMMUNOLOGY, Vol: 42, Pages: 1283-1292, ISSN: 0161-5890
Sabbattini P, Dillon N, 2005, The lambda 5-VpreB1 locus - a model system for studying gene regulation during early B cell development, SEMINARS IN IMMUNOLOGY, Vol: 17, Pages: 121-127, ISSN: 1044-5323
Sabbattini P, Lundgren M, Georgiou A, et al., 2001, Binding of Ikaros to the lambda 5 promoter silences transcription through a mechanism that does not require heterochromatin formation, EMBO JOURNAL, Vol: 20, Pages: 2812-2822, ISSN: 0261-4189
Lundgren M, Chow CM, Sabbattini P, et al., 2000, Transcription factor dosage affects changes in higher order chromatin structure associated with activation of a heterochromatic gene, CELL, Vol: 103, Pages: 733-743, ISSN: 0092-8674
Dillon N, Sabbattini P, 2000, Functional gene expression domains: defining the functional unit of eukaryotic gene regulation, BIOESSAYS, Vol: 22, Pages: 657-665, ISSN: 0265-9247
Sabbattini P, Georgiou A, Sinclair C, et al., 1999, Analysis of mice with single and multiple copies of transgenes reveals a novel arrangement for the lambda 5-V-preB1 locus control region, MOLECULAR AND CELLULAR BIOLOGY, Vol: 19, Pages: 671-679, ISSN: 0270-7306
Sabbattini P, Six E, Zangrossi S, et al., 1996, Immunity specificity determinants in the P4-like retronphage phi R73, Virology, Vol: 216, Pages: 389-396
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