A crucial role of the ubiquitously expressed transcription factor Sp1 at early stages of hematopoietic specification [array]

ABSTRACT: Mammalian development is regulated by the interplay of tissue-specific and ubiquitously expressed transcription factors, such as Sp1. Sp1 knock-out mice die in utero with multiple phenotypic aberrations, but the underlying molecular mechanism of this differentiation failure has been elusive. Here we used conditional knock-out mice as well as the differentiation of mouse ES cells as a model to address this issue. To this end we examined differentiation potential, global gene expression patterns and Sp1 target regions in Sp1 wild-type and deficient cells representing different stages of hematopoiesis. Sp1-/- cells progress through most embryonic stages of blood cell development but cannot complete terminal differentiation. For most Sp1 target and non-target genes, gene expression is unaffected by Sp1 inactivation. However, Cdx and multiple Hox genes are stage-specific targets of Sp1 and are down-regulated at an early stage. As a consequence, expression of genes involved in hematopoietic specification are progressively deregulated, highlighting the regulatory hierarchy of hematopoietic specification. Our work demonstrates that the early absence of active Sp1 sets a cascade in motion that culminates in a failure of terminal hematopoietic differentiation and emphasizes the role of ubiquitously expressed transcription factors for tissue-specific gene regulation. Microarray expression data, 16 arrays with 2 independent biological replicates (8 arrays wildtype and 8 arrays knock out) obtained from differentiation of ES cells to study the transcription factor Sp1 activity at early stages of early hematopoietic specification.

ORGANISM(S): Mus musculus

SUBMITTER: Salam Assi 

PROVIDER: E-GEOD-52497 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress