Foxh1 Occupies cis-Regulatory Modules Prior to Dynamic Transcription Factor Interactions Controlling the Mesendoderm Gene Program.
The interplay between transcription factors and chromatin dictates gene regulatory network activity. Germ layer specification is tightly coupled with zygotic gene activation and, in most metazoans, is dependent upon maternal factors. We explore the dynamic genome-wide interactions of Foxh1, a maternal transcription factor that mediates Nodal/TGF-β signaling, with cis-regulatory modules (CRMs) during mesendodermal specification. Foxh1 marks CRMs during cleavage stages and recruits the co-repressor Tle/Groucho in the early blastula. We highlight a population of CRMs that are continuously occupied by Foxh1 and show that they are marked by H3K4me1, Ep300, and Fox/Sox/Smad motifs, suggesting interplay between these factors in gene regulation. We also propose a molecular "hand-off" between maternal Foxh1 and zygotic Foxa at these CRMs to maintain enhancer activation. Our findings suggest that Foxh1 functions at the top of a hierarchy of interactions by marking developmental genes for activation, beginning with the onset of zygotic gene expression.
Department of Developmental and Cell Biology, Ayala School of Biological Sciences, University of California, Irvine, CA 92697, USA.
Rebekah M
RM
Charney
Department of Computer Science, Donald Bren School of Information & Computer Sciences, University of California, Irvine, CA 92697, USA.
Elmira
E
Forouzmand
Department of Developmental and Cell Biology, Ayala School of Biological Sciences, University of California, Irvine, CA 92697, USA.
Jin Sun
JS
Cho
Department of Developmental and Cell Biology, Ayala School of Biological Sciences, University of California, Irvine, CA 92697, USA.
Jessica
J
Cheung
Department of Developmental and Cell Biology, Ayala School of Biological Sciences, University of California, Irvine, CA 92697, USA.
Kitt D
KD
Paraiso
Marine Genomics Unit, Okinawa Institute of Science and Technology Graduate University, 1919-1 Tancha, Onna-son, Okinawa 904-0495, Japan.
Yuuri
Y
Yasuoka
Institute for Amphibian Biology, Graduate School of Science, Hiroshima University, 1-3-1 Kagamiyama, Higashihiroshima, Hiroshima 739-8526, Japan.
Shuji
S
Takahashi
Department of Biological Sciences, Graduate School of Science, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Masanori
M
Taira
Department of Developmental and Cell Biology, Ayala School of Biological Sciences, University of California, Irvine, CA 92697, USA.
Ira L
IL
Blitz
Department of Computer Science, Donald Bren School of Information & Computer Sciences, University of California, Irvine, CA 92697, USA.
Xiaohui
X
Xie
Department of Developmental and Cell Biology, Ayala School of Biological Sciences, University of California, Irvine, CA 92697, USA. Electronic address: kwcho@uci.edu.
Ken W Y
KW
Cho
D000818:Animals; D036703:Blastula / Q000378:metabolism; D002970:Cleavage Stage, Ovum / Q000378:metabolism; D056970:Co-Repressor Proteins / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000378:metabolism; D004707:Endoderm / Q000196:embryology / Q000378:metabolism*; D004742:Enhancer Elements, Genetic / Q000235:genetics; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D016678:Genome; D006657:Histones / Q000378:metabolism; D008239:Lysine / Q000378:metabolism; D008648:Mesoderm / Q000196:embryology / Q000378:metabolism*; D008745:Methylation; D055457:Nodal Protein / Q000378:metabolism; D011485:Protein Binding / Q000235:genetics; D012319:RNA Polymerase II / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics; D017423:Sequence Analysis, RNA; D015398:Signal Transduction / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D014981:Xenopus / Q000196:embryology* / Q000235:genetics* / Q000378:metabolism; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism*
D056970:Co-Repressor Proteins; C102067:FOXH1 protein, Xenopus; D051858:Forkhead Transcription Factors; D006657:Histones; D055457:Nodal Protein; D012333:RNA, Messenger; D014157:Transcription Factors; D029867:Xenopus Proteins; D012319:RNA Polymerase II; D008239:Lysine
ChIP-seq; Foxa; Smad2/3; Sox7; Tle/Groucho; Xenopus tropicalis; epigenetics; germ layer specification; histone modifications; pioneer factor