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Chunk #15 — GENOME-WIDE MAPPING OF BAF COMPLEXES

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Mammalian SWI/SNF chromatin remodeling complexes and cancer: Mechanistic insights gained from human genomics.
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Murine genetics in concert with genome-wide binding studies have been informative for understanding features of the mechanism of action of these complexes. The complexes bind over the genome in rather large peaks covering about 2 to 4 kb (50). There are generally about 20,000 to 40,000 sites on chromatin in murine ES cells, lymphocytes, neurons, and some cell lines (50, 51). The number of peaks obtained varies, likely due to the quality of the antibodies and their signal-to-noise ratios. Because the complexes are so frequently inactivated in long-term cell lines, one must be aware that the location and number of binding sites in these lines might reflect a dysfunctional (albeit mechanistically informative) complex. There are about 300,000 BAF complexes per cell in murine ES cells, and it seems that about half of these are chromatin-associated, meaning that each BAF peak must reflect the binding of about 5 or 10 complexes with an average footprint of about 2 to 4 kb (47, 50). This is consistent with the size of the 2-MDa complex, which is about 12 times the molecular weight of a nucleosome (though often misillustrated in reviews as being smaller than a nucleosome).