Related Experiment Video
Updated: May 27, 2026

HOX Loci Focused CRISPR/sgRNA Library Screening Identifying Critical CTCF Boundaries
Published on: March 31, 2019
Myc and Miz-1 have coordinate genomic functions including targeting Hox genes in human embryonic stem cells
Natalia Varlakhanova1, Rebecca Cotterman, Keith Bradnam
1Department of Cell Biology and Human Anatomy, University of California Davis School of Medicine, Sacramento, CA, USA. knoepfler@ucdavis.edu.
Background:
A proposed role for Myc in maintaining mouse embryonic stem (ES) cell pluripotency is transcriptional repression of key differentiation-promoting genes, but detail of the mechanism has remained an important open topic.
Results:
To test the hypothesis that the zinc finger protein Miz-1 plays a central role, in the present work we conducted chromatin immunoprecipitation/microarray (ChIP-chip) analysis of Myc and Miz-1 in human ES cells, finding homeobox (Hox) genes as the most significant functional class of Miz-1 direct targets. Miz-1 differentiation-associated target genes specifically lack acetylated lysine 9 and trimethylated lysine 4 of histone H3 (AcH3K9 and H3K4me3) 9 histone marks, consistent with a repressed transcriptional state. Almost 30% of Miz-1 targets are also bound by Myc and these cobound genes are mostly factors that promote differentiation including Hox genes. Knockdown of Myc increased expression of differentiation genes directly bound by Myc and Miz-1, while a subset of the same genes is downregulated by Miz-1 loss-of-function. Myc and Miz-1 proteins interact with each other and associate with several corepressor factors in ES cells, suggesting a mechanism of repression of differentiation genes.
Conclusions:
Taken together our data indicate that Miz-1 and Myc maintain human ES cell pluripotency by coordinately suppressing differentiation genes, particularly Hox genes. These data also support a new model of how Myc and Miz-1 function on chromatin.
Related Concept Videos
Induced Pluripotent Stem Cells
Somatic cells are...
Combinatorial Gene Control
The expression of more than 30,000 genes is controlled by approximately 2000-3000 transcription factors. This is possible because a single transcription factor can recognize more than one regulatory sequence. The specificity in gene...
Somatic to iPS Cell Reprogramming
Master Transcription Regulators
Methods of Nuclear Reprogramming
Zygotic Development And Stem Cell Formation

