Chromatin modifications in hematopoietic multipotent and committed progenitors are independent of gene subnuclear positioning relative to repressive compartments.
To further clarify the contribution of nuclear architecture in the regulation of gene expression patterns during differentiation of human multipotent cells, we analyzed expression status, histone modifications, and subnuclear positioning relative to repressive compartments, of hematopoietic loci in multipotent and lineage-committed primary human hematopoietic progenitors. We report here that positioning of lineage-affiliated loci relative to pericentromeric heterochromatin compartments (PCH) is identical in multipotent cells from various origins and is unchanged between multipotent and lineage-committed hematopoietic progenitors. However, during differentiation of multipotent hematopoietic progenitors, changes in gene expression and histone modifications at these loci occur in committed progenitors, prior to changes in gene positioning relative to pericentromeric heterochromatin compartments, detected at later stages in precursor and mature cells. Therefore, during normal human hematopoietic differentiation, changes in gene subnuclear location relative to pericentromeric heterochromatin appear to be dictated by whether the gene will be permanently silenced or activated, rather than being predictive of commitment toward a given lineage.
Guillemin
Claire
C
Institut Cochin, Université Paris Descartes, Centre National de la Recherche Scientifique, UMR, Paris, France.
Maleszewska
Marta
M
Guais
Adeline
A
Maës
Jérôme
J
Rouyez
Marie-Christine
MC
Yacia
Azzedine
A
Fichelson
Serge
S
Goodhardt
Michele
M
Francastel
Claire
C
D000107:Acetylation; D000818:Animals; D002451:Cell Compartmentation; D002454:Cell Differentiation / Q000235:genetics; D019070:Cell Lineage; D002843:Chromatin / Q000378:metabolism*; D041905:Erythroid Cells / Q000378:metabolism; D023061:Gene Order; D005914:Globins / Q000378:metabolism; D006410:Hematopoiesis / Q000235:genetics; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D006801:Humans; D007145:Immunoglobulin kappa-Chains / Q000235:genetics; D007223:Infant; D051379:Mice; D039902:Multipotent Stem Cells / Q000166:cytology / Q000378:metabolism*
D002843:Chromatin; D006657:Histones; D007145:Immunoglobulin kappa-Chains; D005914:Globins