Mef2C is a Lineage-restricted Target of Scl/Tal1 and Regulates Megakaryopoiesis and B-cell Homeostasis

Overview

Journal Blood

Publisher Elsevier

Specialty Hematology

Date 2009 Feb 13

PMID 19211936

Citations 27

Authors

Christos Gekas

Katrin E Rhodes

Laurraine M Gereige

Hildur Helgadottir

Roberto Ferrari

Siavash K Kurdistani

Encarnacion Montecino-Rodriguez

Rhonda Bassel-Duby

Eric Olson

Andrei V Krivtsov

Scott Armstrong

Stuart H Orkin

Matteo Pellegrini

Hanna K A Mikkola

Affiliations

Soon will be listed here.

Abstract

The basic helix-loop-helix transcription factor stem cell leukemia gene (Scl) is a master regulator for hematopoiesis essential for hematopoietic specification and proper differentiation of the erythroid and megakaryocyte lineages. However, the critical downstream targets of Scl remain undefined. Here, we identified a novel Scl target gene, transcription factor myocyte enhancer factor 2 C (Mef2C) from Scl(fl/fl) fetal liver progenitor cell lines. Analysis of Mef2C(-/-) embryos showed that Mef2C, in contrast to Scl, is not essential for specification into primitive or definitive hematopoietic lineages. However, adult VavCre(+)Mef2C(fl/fl) mice exhibited platelet defects similar to those observed in Scl-deficient mice. The platelet counts were reduced, whereas platelet size was increased and the platelet shape and granularity were altered. Furthermore, megakaryopoiesis was severely impaired in vitro. Chromatin immunoprecipitation microarray hybridization analysis revealed that Mef2C is directly regulated by Scl in megakaryocytic cells, but not in erythroid cells. In addition, an Scl-independent requirement for Mef2C in B-lymphoid homeostasis was observed in Mef2C-deficient mice, characterized as severe age-dependent reduction of specific B-cell progenitor populations reminiscent of premature aging. In summary, this work identifies Mef2C as an integral member of hematopoietic transcription factors with distinct upstream regulatory mechanisms and functional requirements in megakaryocyte and B-lymphoid lineages.

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