The Kruppel-like Factor KLF4 is a Critical Regulator of Monocyte Differentiation

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 2007 Sep 1

PMID 17762869

Citations 173

Authors

Mark W Feinberg

Akm Khyrul Wara

Zhuoxiao Cao

Maria A Lebedeva

Frank Rosenbauer

Hiromi Iwasaki

Hideyo Hirai

Jonathan P Katz

Richard L Haspel

Susan Gray

Koichi Akashi

Julie Segre

Klaus H Kaestner

Daniel G Tenen

Mukesh K Jain

Affiliations

Soon will be listed here.

Abstract

Monocyte differentiation involves the participation of lineage-restricted transcription factors, although the mechanisms by which this process occurs are incompletely defined. Within the hematopoietic system, members of the Kruppel-like family of factors (KLFs) play essential roles in erythrocyte and T lymphocyte development. Here we show that KLF4/GKLF is expressed in a monocyte-restricted and stage-specific pattern during myelopoiesis and functions to promote monocyte differentiation. Overexpression of KLF4 in HL-60 cells confers the characteristics of mature monocytes. Conversely, KLF4 knockdown blocked phorbol ester-induced monocyte differentiation. Forced expression of KLF4 in primary common myeloid progenitors (CMPs) or hematopoietic stem cells (HSCs) induced exclusive monocyte differentiation in clonogenic assays, whereas KLF4 deficiency inhibited monocyte but increased granulocyte differentiation. Mechanistic studies demonstrate that KLF4 is a target gene of PU.1. Consistently, KLF4 can rescue PU.1-/- fetal liver cells along the monocytic lineage and can activate the monocytic-specific CD14 promoter. Thus, KLF4 is a critical regulator in the transcriptional network controlling monocyte differentiation.

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