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Article: Transcriptional regulation of the Ikzf1 locus

TitleTranscriptional regulation of the Ikzf1 locus
Authors
KeywordsAnimals
B-Lymphocytes/metabolism
Base Sequence
Binding Sites/genetics
Brain/metabolism
Enhancer Elements, Genetic/*genetics
Epigenesis, Genetic
Flow Cytometry
Gene Regulatory Networks
Green Fluorescent Proteins/genetics/metabolism
Ikaros Transcription Factor/*genetics/metabolism
Issue Date2013
PublisherAmerican Society of Hematology. The Journal's web site is located at http://bloodjournal.hematologylibrary.org/
Citation
Blood, 2013, v. 122 n. 18, p. 3149-3159 How to Cite?
AbstractIkaros is a critical regulator of lymphocyte development and homeostasis; thus, understanding its transcriptional regulation is important from both developmental and clinical perspectives. Using a mouse transgenic reporter approach, we functionally characterized a network of highly conserved cis-acting elements at the Ikzf1 locus. We attribute B-cell and myeloid but not T-cell specificity to the main Ikzf1 promoter. Although this promoter was unable to counter local chromatin silencing effects, each of the 6 highly conserved Ikzf1 intronic enhancers alleviated silencing. Working together, the Ikzf1 enhancers provided locus control region activity, allowing reporter expression in a position and copy-independent manner. Only 1 of the Ikzf1 enhancers was responsible for the progressive upregulation of Ikaros expression from hematopoietic stem cells to lymphoid-primed multipotent progenitors to T-cell precursors, which are stages of differentiation dependent on Ikaros for normal outcome. Thus, Ikzf1 is regulated by both epigenetic and transcriptional factors that target its enhancers in both redundant and specific fashions to provide an expression profile supportive of normal lymphoid lineage progression and homeostasis. Mutations in the Ikzf1 regulatory elements and their interacting factors are likely to have adverse effects on lymphopoiesis and contribute to leukemogenesis.
Persistent Identifierhttp://hdl.handle.net/10722/219916
ISSN
2015 Impact Factor: 11.841
2015 SCImago Journal Rankings: 6.395
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorYoshida, T-
dc.contributor.authorLandhuis, E-
dc.contributor.authorDose, M-
dc.contributor.authorHazan, I-
dc.contributor.authorZhang, J-
dc.contributor.authorNaito, T-
dc.contributor.authorJackson, AF-
dc.contributor.authorWu, J-
dc.contributor.authorPerotti, EA-
dc.contributor.authorKaufmann, C-
dc.contributor.authorGounari, F-
dc.contributor.authorMorgan, BA-
dc.contributor.authorGeorgopoulos, K-
dc.date.accessioned2015-10-02T07:58:32Z-
dc.date.available2015-10-02T07:58:32Z-
dc.date.issued2013-
dc.identifier.citationBlood, 2013, v. 122 n. 18, p. 3149-3159-
dc.identifier.issn0006-4971-
dc.identifier.urihttp://hdl.handle.net/10722/219916-
dc.description.abstractIkaros is a critical regulator of lymphocyte development and homeostasis; thus, understanding its transcriptional regulation is important from both developmental and clinical perspectives. Using a mouse transgenic reporter approach, we functionally characterized a network of highly conserved cis-acting elements at the Ikzf1 locus. We attribute B-cell and myeloid but not T-cell specificity to the main Ikzf1 promoter. Although this promoter was unable to counter local chromatin silencing effects, each of the 6 highly conserved Ikzf1 intronic enhancers alleviated silencing. Working together, the Ikzf1 enhancers provided locus control region activity, allowing reporter expression in a position and copy-independent manner. Only 1 of the Ikzf1 enhancers was responsible for the progressive upregulation of Ikaros expression from hematopoietic stem cells to lymphoid-primed multipotent progenitors to T-cell precursors, which are stages of differentiation dependent on Ikaros for normal outcome. Thus, Ikzf1 is regulated by both epigenetic and transcriptional factors that target its enhancers in both redundant and specific fashions to provide an expression profile supportive of normal lymphoid lineage progression and homeostasis. Mutations in the Ikzf1 regulatory elements and their interacting factors are likely to have adverse effects on lymphopoiesis and contribute to leukemogenesis.-
dc.languageeng-
dc.publisherAmerican Society of Hematology. The Journal's web site is located at http://bloodjournal.hematologylibrary.org/-
dc.relation.ispartofBlood-
dc.rightsThis research was originally published in The Hematologist: ASH News and Reports. Author(s). Title. The Hematologist: ASH News and Reports. Year;Vol,Issue:pp-pp. © the American Society of Hematology.-
dc.subjectAnimals-
dc.subjectB-Lymphocytes/metabolism-
dc.subjectBase Sequence-
dc.subjectBinding Sites/genetics-
dc.subjectBrain/metabolism-
dc.subjectEnhancer Elements, Genetic/*genetics-
dc.subjectEpigenesis, Genetic-
dc.subjectFlow Cytometry-
dc.subjectGene Regulatory Networks-
dc.subjectGreen Fluorescent Proteins/genetics/metabolism-
dc.subjectIkaros Transcription Factor/*genetics/metabolism-
dc.titleTranscriptional regulation of the Ikzf1 locus-
dc.typeArticle-
dc.identifier.emailZhang, J: jzhang1@hku.hk-
dc.identifier.authorityZhang, J=rp01713-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1182/blood-2013-01-474916-
dc.identifier.pmid24002445-
dc.identifier.pmcidPMC3814732-
dc.identifier.scopuseid_2-s2.0-84888246827-
dc.identifier.volume122-
dc.identifier.issue18-
dc.identifier.spage3149-
dc.identifier.epage3159-
dc.identifier.isiWOS:000326503200014-
dc.publisher.placeUnited States-

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