A global role for KLF1 in erythropoiesis revealed by ChIP-seq in primary erythroid cells.
KLF1 regulates a diverse suite of genes to direct erythroid cell differentiation from bipotent progenitors. To determine the local cis-regulatory contexts and transcription factor networks in which KLF1 operates, we performed KLF1 ChIP-seq in the mouse. We found at least 945 sites in the genome of E14.5 fetal liver erythroid cells which are occupied by endogenous KLF1. Many of these recovered sites reside in erythroid gene promoters such as Hbb-b1, but the majority are distant to any known gene. Our data suggests KLF1 directly regulates most aspects of terminal erythroid differentiation including production of alpha- and beta-globin protein chains, heme biosynthesis, coordination of proliferation and anti-apoptotic pathways, and construction of the red cell membrane and cytoskeleton by functioning primarily as a transcriptional activator. Additionally, we suggest new mechanisms for KLF1 cooperation with other transcription factors, in particular the erythroid transcription factor GATA1, to maintain homeostasis in the erythroid compartment.
Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4072, Australia.
Michael R
MR
Tallack
Tom
T
Whitington
Wai Shan
WS
Yuen
Elanor N
EN
Wainwright
Janelle R
JR
Keys
Brooke B
BB
Gardiner
Ehsan
E
Nourbakhsh
Nicole
N
Cloonan
Sean M
SM
Grimmond
Timothy L
TL
Bailey
Andrew C
AC
Perkins
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001483:Base Sequence; D003599:Cytoskeleton / Q000235:genetics; D004910:Erythrocyte Membrane / Q000235:genetics; D041905:Erythroid Cells / Q000378:metabolism*; D004920:Erythropoiesis / Q000235:genetics*; D050982:GATA1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D005914:Globins / Q000096:biosynthesis / Q000235:genetics; D006418:Heme / Q000096:biosynthesis / Q000235:genetics; D051741:Kruppel-Like Transcription Factors / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic
D050982:GATA1 Transcription Factor; C494689:Gata1 protein, mouse; D051741:Kruppel-Like Transcription Factors; C080774:erythroid Kruppel-like factor; D006418:Heme; D005914:Globins