CDK9/cyclin complexes modulate endoderm induction by direct interaction with Mix.3/mixer.
Mix-related homeodomain proteins are involved in endoderm formation in the early vertebrate embryo. We used a yeast two-hybrid screen to identify proteins that interact with Mix.3/mixer to regulate endoderm induction. We demonstrate that cyclin-dependent kinase 9 (CDK9) interacts with the carboxyl terminal domain of Mix.3. CDK9 is the catalytic subunit of the PTEF-b transcription elongation complex that phosphorylates the C-terminal domain of RNA polymerase II to promote efficient elongation of nascent transcripts. Using whole embryo transcription reporter and animal pole explant assays, we show that Mix.3 activity is regulated by CDK9/cyclin complexes. Co-expression of cyclin T2 and cyclin K had different effects on Mix.3 transcriptional activity and endoderm induction. Our data suggest that binding of CDK9, and the recruitment of different cyclin partners, can modulate the endoderm-inducing activity of Mix.3 during embryonic development. Developmental Dynamics 238:1346-1357, 2009. (c) 2009 Wiley-Liss, Inc.
Department of Pathology, St Jude Children's Research Hospital, Memphis, Tennessee, USA.
Haiqing
H
Zhu
Joanne R
JR
Doherty
Emin
E
Kuliyev
Paul E
PE
Mead
D000595:Amino Acid Sequence; D000818:Animals; D042863:Cyclin-Dependent Kinase 9 / Q000235:genetics / Q000378:metabolism*; D016213:Cyclins / Q000235:genetics / Q000378:metabolism*; D004627:Embryonic Induction; D004707:Endoderm / Q000502:physiology*; D005326:Fetal Proteins / Q000235:genetics / Q000378:metabolism; D017930:Genes, Reporter; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D017403:In Situ Hybridization; D008969:Molecular Sequence Data; D011485:Protein Binding; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D020798:Two-Hybrid System Techniques; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis / Q000033:anatomy & histology / Q000196:embryology / Q000378:metabolism; D000098908:Brachyury Protein
D042863:Cyclin-Dependent Kinase 9; D016213:Cyclins; D005326:Fetal Proteins; D018398:Homeodomain Proteins; D020033:Protein Isoforms; D020825:T-Box Domain Proteins; D014157:Transcription Factors; D029867:Xenopus Proteins; D000098908:Brachyury Protein; C405705:mixer protein, Xenopus