Plzf mediates transcriptional repression of HoxD gene expression through chromatin remodeling.
The molecular mechanisms that regulate coordinated and colinear activation of Hox gene expression in space and time remain poorly understood. Here we demonstrate that Plzf regulates the spatial expression of the AbdB HoxD gene complex by binding to regulatory elements required for restricted Hox gene expression and can recruit histone deacetylases to these sites. We show by scanning forced microscopy that Plzf, via homodimerization, can form DNA loops and bridge distant Plzf binding sites located within HoxD gene regulatory elements. Furthermore, we demonstrate that Plzf physically interacts with Polycomb proteins on DNA. We propose a model by which the balance between activating morphogenic signals and transcriptional repressors such as Plzf establishes proper Hox gene expression boundaries in the limb bud.
Barna
Maria
M
Molecular Biology Program, Department of Pathology, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Merghoub
Taha
T
Costoya
José A
JA
Ruggero
Davide
D
Branford
Matthew
M
Bergia
Anna
A
Samori
Bruno
B
Pandolfi
Pier Paolo
PP
D000818:Animals; D002843:Chromatin / Q000235:genetics* / Q000378:metabolism / Q000648:ultrastructure; D004247:DNA / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D006657:Histones / Q000235:genetics / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics*; D051741:Kruppel-Like Transcription Factors; D051379:Mice; D018625:Microscopy, Atomic Force; D063146:Polycomb-Group Proteins; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D012097:Repressor Proteins / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic
D002843:Chromatin; D004268:DNA-Binding Proteins; D006657:Histones; D018398:Homeodomain Proteins; D051741:Kruppel-Like Transcription Factors; D063146:Polycomb-Group Proteins; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D012097:Repressor Proteins; D014157:Transcription Factors; C513267:Zbtb16 protein, mouse; D004247:DNA