The L2a element is a mouse CD8 silencer that interacts with MAR-binding proteins SATB1 and CDP.

Previous transgenic-reporter and targeted-deletion studies indicate that the subset-specific expression of CD8αβ heterodimers is controlled by multiple enhancer activities, since no silencer elements had been found within the locus. We have identified such a silencer as L2a, a previously characterized ∼ 220 bp nuclear matrix associating region (MAR) located ∼ 4.5 kb upstream of CD8α.

Foxp1 is an essential transcriptional regulator for the generation of quiescent naive T cells during thymocyte development.

Proper thymocyte development is required to establish T-cell central tolerance and to generate naive T cells, both of which are essential for T-cell homeostasis and a functional immune system. Here we demonstrate that the loss of transcription factor Foxp1 results in the abnormal development of T cells. Instead of generating naive T cells, Foxp1-deficient single-positive thymocytes acquire an activated phenotype prematurely in the thymus and lead to the generation of peripheral CD4(+) T and CD8(+) T cells that exhibit an activated phenotype and increased apoptosis and readily produce cytokines upon T-cell receptor engagement.

Developmental and species-divergent globin switching are driven by BCL11A.

The contribution of changes in cis-regulatory elements or trans-acting factors to interspecies differences in gene expression is not well understood. The mammalian beta-globin loci have served as a model for gene regulation during development. Transgenic mice containing the human beta-globin locus, consisting of the linked embryonic (epsilon), fetal (gamma) and adult (beta) genes, have been used as a system to investigate the temporal switch from fetal to adult haemoglobin, as occurs in humans.

SATB1 is required for CD8 coreceptor reversal.

Intrathymic signals induce the differentiation of immature CD4(+)CD8(+) double positive (DP) thymocytes into mature CD4(+) or CD8(+) single positive (SP) T cells. The transcriptional mechanism by which CD8 lineage is determined is not fully understood. The best evidence, which favors the kinetic signaling/coreceptor reversal model, indicates that signaled DP thymocytes terminate CD8 transcription prior to their subsequent re-initiation of CD8 transcription and ultimate differentiation into CD8SP T cells.

Epitope tagging of proteins at the native chromosomal loci of genes in mice and in cultured vertebrate cells.

Adding epitope tags to proteins is an important method for biochemical analyses and is generally accomplished in metazoan cells using ectopically expressed, tagged trans-genes. In Saccharomyces cerevisiae, the addition of epitope tags to proteins is easily achieved at the genomic locus of a gene of interest due to the high efficiency of homologous recombination in that organism. Most metazoan cells do not exhibit this high homologous recombination efficiency, and therefore trans-genes with in-frame epitope tags are used.

A role for SATB1, a nuclear matrix association region-binding protein, in the development of CD8SP thymocytes and peripheral T lymphocytes.

Studies have suggested that binding of the SATB1 protein to L2a, a matrix association region located 4.5 kb 5' to the mouse CD8alpha gene, positively affects CD8 expression in T cells. Therefore, experiments were performed to determine the effect on T cell development of reduced expression of SATB1.

Bop encodes a muscle-restricted protein containing MYND and SET domains and is essential for cardiac differentiation and morphogenesis.

Many transcription factors regulate specific temporal-spatial events during cardiac differentiation; however, the mechanisms that regulate such events are largely unknown. Using a modified subtractive hybridization method to identify specific genes that influence early cardiac development, we found that Bop is expressed specifically in cardiac and skeletal muscle precursors before differentiation of these lineages. Bop encodes a protein containing MYND and SET domains, which have been shown to regulate transcription by mediating distinct chromatin modifications.