Project description:B-type lamins, the major structural component of the nuclear lamina, is thought to play a repressive role in the expression of many of its bound genes whose silencing are known to be critical for cell differentiation during early development. Using global mapping of lamin-B-chromatin interaction, we find that the binding to lamin-B indeed correlated with gene silencing in mouse embryonic stem cells (ESC) and ESC-derived trophectoderm (TE) lineage cells. To address whether lamin-B directly suppresses the expression of the bound genes, we have derived ESCs from lamin-B-null mouse blastocysts. Unexpectedly, microarray analyses of ESCs and TE cells show that B-type lamins do not repress the expression of their bound genes. Furthermore, the knockout mice that do not express any B-type lamins can develop to term but exhibit small body size and perinatal lethality. Our studies demonstrate that B-type lamins are not required for cell differentiation during early embryonic development. Instead, they are required for proper late embryonic and perinatal development. The availability of the null ESCs and mice opens the door to further define the functions of B-type lamins.
Project description:Chromatin binding profiling showed that dHey binds to enhancers in order to maintain EC identity, and co-regulates nuclear organization by governing a switch in the expression of nuclear lamins. Moreover, like dHey loss, de-regulated expression of lamins override identity programs. Thus, a single TF concomitantly orchestrates chromatin state, enhancer activity, and nuclear organization safeguarding differentiated cell identity Chromatin profiling using Dam-dHey shows preferential recruitment to enhancers and transcriptionally active regions. Manuscript title: Specification and maintenance of enterocyte identity requires dHey and nuclear lamins
Project description:Introgressed variants from other species can be an important source of genetic variation because they may arise rapidly, can include multiple mutations on a single haplotype, and have often been pretested by selection in the species of origin. Although introgressed alleles are generally deleterious, several studies have reported introgression as the source of adaptive alleles-including the rodenticide-resistant variant of Vkorc1 that introgressed from Mus spretus into European populations of Mus musculus domesticus. Here, we conducted bidirectional genome scans to characterize introgressed regions into one wild population of M. spretus from Spain and three wild populations of M. m. domesticus from France, Germany, and Iran. Despite the fact that these species show considerable intrinsic postzygotic reproductive isolation, introgression was observed in all individuals, including in the M. musculus reference genome (GRCm38). Mus spretus individuals had a greater proportion of introgression compared with M. m. domesticus, and within M. m. domesticus, the proportion of introgression decreased with geographic distance from the area of sympatry. Introgression was observed on all autosomes for both species, but not on the X-chromosome in M. m. domesticus, consistent with known X-linked hybrid sterility and inviability genes that have been mapped to the M. spretus X-chromosome. Tract lengths were generally short with a few outliers of up to 2.7 Mb. Interestingly, the longest introgressed tracts were in olfactory receptor regions, and introgressed tracts were significantly enriched for olfactory receptor genes in both species, suggesting that introgression may be a source of functional novelty even between species with high barriers to gene flow.
Project description:A transcriptome study in mouse hematopoietic stem cells was performed using a sensitive SAGE method, in an attempt to detect medium and low abundant transcripts expressed in these cells. Among a total of 31,380 unique transcript, 17,326 (55%) known genes were detected, 14,054 (45%) low-copy transcripts that have no matches to currently known genes. 3,899 (23%) were alternatively spliced transcripts of the known genes and 3,754 (22%) represent anti-sense transcripts from known genes.