Abstract
The Zinc-finger protein of the cerebellum 2 (Zic2) is one of the vertebrate homologs of the Drosophila pair-rule gene odd-paired (opa). Our molecular and biochemical studies demonstrate that Zic2 preferentially binds to transcriptional enhancers and is required for the regulation of gene expression in embryonic stem cells. Detailed genome-wide and molecular studies reveal that Zic2 can function with Mbd3/NuRD in regulating the chromatin state and transcriptional output of genes linked to differentiation. Zic2 is required for proper differentiation of embryonic stem cells (ESCs), similar to what has been previously reported for Mbd3/NuRD. Our study identifies Zic2 as a key factor in the execution of transcriptional fine-tuning with Mbd3/NuRD in ESCs through interactions with enhancers. Our study also points to the role of the Zic family of proteins as enhancer-specific binding factors functioning in development.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 685-694 |
| Number of pages | 10 |
| Journal | Molecular cell |
| Volume | 57 |
| Issue number | 4 |
| DOIs | |
| State | Published - Feb 19 2015 |
Funding
We thank the Molecular Biology core facility at the Stowers Institute for creating and sequencing libraries for next-generation sequencing and the Stowers Tissue Culture facility for large-scale cell culture and establishment of stable cell lines. We thank Alex Garruss for the initial analysis of the ChIP-seq and RNA-seq data. We thank Laura Shilatifard and Lisa Kennedy for editorial assistance. Z.L. is a Fellow of the Leukemia and Lymphoma Society. These studies were supported in part by grants R01GM069905 and R01CA89455 from the National Cancer Institute to A.S.
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology