Antisense Activity across the Promoter is Required for -Mediated Silencing in the Imprinted Cluster.

Macro long non-coding RNAs (lncRNAs) play major roles in gene silencing in inprinted gene clusters. Within the imprinted cluster, the paternally expressed lncRNA downregulates its sense counterpart . To explore the mechanism of action of , we generated two new knock-in alleles to truncate upstream and downstream of the promoter.

Nonredundant roles for Runx1 alternative promoters reflect their activity at discrete stages of developmental hematopoiesis.

The transcription factor Runx1 is a pivotal regulator of definitive hematopoiesis in mouse ontogeny. Vertebrate Runx1 is transcribed from 2 promoters, the distal P1 and proximal P2, which provide a paradigm of the complex transcriptional and translational control of Runx1 function. However, very little is known about the biologic relevance of alternative Runx1 promoter usage in definitive hematopoietic cell emergence.

Runx genes are direct targets of Scl/Tal1 in the yolk sac and fetal liver.

Transcription factors such as Scl/Tal1, Lmo2, and Runx1 are essential for the development of hematopoietic stem cells (HSCs). However, the precise mechanisms by which these factors interact to form transcriptional networks, as well as the identity of the genes downstream of these regulatory cascades, remain largely unknown. To this end, we generated an Scl(-/-) yolk sac cell line to identify candidate Scl target genes by global expression profiling after reintroduction of a TAT-Scl fusion protein.

Runx1-mediated hematopoietic stem-cell emergence is controlled by a Gata/Ets/SCL-regulated enhancer.

The transcription factor Runx1/AML1 is an important regulator of hematopoiesis and is critically required for the generation of the first definitive hematopoietic stem cells (HSCs) in the major vasculature of the mouse embryo. As a pivotal factor in HSC ontogeny, its transcriptional regulation is of high interest but is largely undefined. In this study, we used a combination of comparative genomics and chromatin analysis to identify a highly conserved 531-bp enhancer located at position + 23.

Identification of an imprinting control region affecting the expression of all transcripts in the Gnas cluster.

Genomic imprinting results in allele-specific silencing according to parental origin. Silencing is brought about by imprinting control regions (ICRs) that are differentially marked in gametogenesis. The group of imprinted transcripts in the mouse Gnas cluster (Nesp, Nespas, Gnasxl, Exon 1A and Gnas) provides a model for analyzing the mechanisms of imprint regulation.

From hemangioblast to hematopoietic stem cell: an endothelial connection?

The developmental origin of hematopoietic stem cells has been the subject of much research. Now that the developmental link between the hematopoietic system and the vasculature has been well established, questions remain regarding the precise cellular origin of definitive hematopoietic cells and at what point they branch off from the endothelial lineage. Do they emerge directly from a hemangioblast-type cell, similar to what is proposed for primitive yolk sac hematopoiesis, or are they generated via an endothelial intermediate, the hemogenic endothelium? In this review, we will give an overview of the data obtained from the mouse and avian models on the cellular origins of the hematopoietic system.