Project description:The extreme environments of the Tibetan Plateau offer significant challenges to human survival, demanding novel adaptations. While the role of biological and agricultural adaptations in enabling early human colonization of the plateau has been widely discussed, the contribution of pastoralism is less well understood, especially the dairy pastoralism that has historically been central to Tibetan diets. Here, we analyze preserved proteins from the dental calculus of 40 ancient individuals to report the earliest direct evidence of dairy consumption on the Tibetan Plateau. Our palaeoproteomic results demonstrate that dairy pastoralism began on the higher plateau by approximately 3,500 years ago, more than 2,000 years earlier than the recording of dairying in historical sources. With less than 1% of the Tibetan Plateau dedicated to farmland, pastoralism and the milking of ruminants were essential for large-scale human expansion into agriculturally-marginal regions that make up the majority of the plateau. Dairy pastoralism allowed conversion of abundant grasslands into nutritional human food, which facilitating adaptation in the face of extreme climatic and altitudinal pressures, and maximizing the land area available for long-term human occupation of the “roof of the world”.
Project description:The transcriptome signature of peripheral blood mononuclear cells (PBMCs) of Ladakhi cattle adapted to high altitude vis a vis Sahiwal cattle adapted to the arid/semi-arid region at mean sea level was established using bovine expression microarray chips. The transcriptome analysis of PBMCs from these cattle types living at two distinct altitudes, resulted in identification of several hundred differentially expressed genes, biological processes, molecular functions and pathways.
Project description:Every known SWI/SNF chromatin-remodeling complex incorporates an ARID DNA binding domain-containing subunit. Despite being a ubiquitous component of these complexes, physiological roles for this domain remain undefined. We screened an N-ethyl-N-nitrosurea (ENU) mutagenized library for ARID domain point mutations and generated an Arid1a/Baf250a hypomorphic allele. The mutant ARID1a (V1068G) protein is stably expressed at wild-type levels, and it is capable of assembling into a SWI/SNF complex with in vitro mononucleosome disruption activity. However, its capacity to bind DNA is lost. Consistent with defective DNA binding, mutant protein occupancy at known SWI/SNF target genes is decreased. Loss of DNA binding is associated with concurrent changes in SWI/SNF target gene expression. Mutant embryos manifest heart defects, fail to establish proper yolk sac vasculature, and exhibit hemorrhaging. As a result of these phenotypes, mutant embryos fail to establish proper circulation, culminating in ischemic arrest in utero between days 9.5 and 11.5. These data support a role for ARID1a-containing, BAF-A complexes in heart and extraembryonic vascular development, and indicate the ARID domain of ARID1a is essential in this regard. Hence, intrinsic ARID subunit-DNA interactions are required for normal SWI/SNF function in vivo. Four-condition experiment, wild-type vs Baf250a/Arid1a^V1068G/V1068G yolk sacs isolated at E8.5 and E9.5. Biological replicates: 3 per condition.
Project description:Granulosa cells originating from two different phases of antral follicle growth (plateau and atretic) were compared in follicles with a diameter of 9mm or more. The plateau follicle is the reference.
Project description:Every known SWI/SNF chromatin-remodeling complex incorporates an ARID DNA binding domain-containing subunit. Despite being a ubiquitous component of the complex, physiological roles for this domain remain undefined. Here we show that disruption of ARID1a-DNA binding in mice results in embryonic lethality, with mutant embryos manifesting prominent defects in the heart and extraembryonic vasculature. The DNA binding defective mutant ARID1a subunit is stably expressed and capable of assembling into a SWI/SNF complex with chromatin remodeling activity, but promoter occupancy by ARID1a-containing, SWI/SNF complexes (BAF-A) is impaired. Depletion of ARID domain-dependent, BAF-A associations at THROMBOSPONDIN 1 (THBS1) led to the concomitant upregulation of this anti-angiogenic protein. Using a THBS1 promoter-reporter gene, we further show that BAF-A directly regulates THBS1 promoter activity in an ARID domain-dependent manner. Our data not only demonstrate that ARID-DNA interactions are physiologically relevant in higher eukaryotes, but also indicate these interactions can facilitate SWI/SNF binding to target sites in vivo. These findings support the model wherein cooperative interactions among intrinsic subunit-chromatin interaction domains and sequence-specific transcription factors drive SWI/SNF recruitment.