Stem cell pluripotency and higher-order chromatin structure

We found that the nuclear proteins Satb1 and Satb2, which function as determinants of higher-order chromatin structure, have opposing roles in the regulation of the pluripotency gene Nanog. In particular, Satb1 represses Nanog, whereas the closely related Satb2 protein activates Nanog.

Regulatory circuitry of Satb2 in ES cells

Moreover, both Satb1-deficient ES cells and wild-type ES cells in which Satb2 is overexpressed are more efficient in reprogramming human B lymphocytes in heterokaryon fusion experiments. Recently, we found that SUMOylation of Satb2 during ectodermal differentiation is required for the down-regulation of pluripotency genes. Satb2 also plays a role in B lymphocytes by binding to AT-rich sequences that flank the intrinsic immunoglobulin heavy chain (IgH) enhancer.

By studying the subnuclear localization and higher-order chromatin structure of the IgH locus in Satb2-deficient pro-B cells, we anticipate to unravel the molecular basis of Satb2 function in the regulation of higher-order chromatin structure. We combine biochemical, imaging and genetic approaches, to elucidate how Satb proteins functionally organize chromatin.

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