NuMA influences higher order chromatin organization in human mammary epithelium.
The coiled-coil protein NuMA is an important contributor to mitotic spindle formation and stabilization. A potential role for NuMA in nuclear organization or gene regulation is suggested by the observations that its pattern of nuclear distribution depends upon cell phenotype and that it interacts and/or colocalizes with transcription factors. To date, the precise contribution of NuMA to nuclear function remains unclear. Previously, we observed that antibody-induced alteration of NuMA distribution in growth-arrested and differentiated mammary epithelial structures (acini) in three-dimensional culture triggers the loss of acinar differentiation. Here, we show that in mammary epithelial cells, NuMA is present in both the nuclear matrix and chromatin compartments. Expression of a portion of the C terminus of NuMA that shares sequence similarity with the chromatin regulator HPC2 is sufficient to inhibit acinar differentiation and results in the redistribution of NuMA, chromatin markers acetyl-H4 and H4K20m, and regions of deoxyribonuclease I-sensitive chromatin compared with control cells. Short-term alteration of NuMA distribution with anti-NuMA C-terminus antibodies in live acinar cells indicates that changes in NuMA and chromatin organization precede loss of acinar differentiation. These findings suggest that NuMA has a role in mammary epithelial differentiation by influencing the organization of chromatin.
Abad
Patricia C
PC
Department of Basic Medical Sciences and Cancer Center, Purdue University, West Lafayette, IN 47907-2026, USA.
Lewis
Jason
J
Mian
I Saira
IS
Knowles
David W
DW
Sturgis
Jennifer
J
Badve
Sunil
S
Xie
Jun
J
Lelièvre
Sophie A
SA
D034961:Antigens, Nuclear / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D018797:Cell Cycle Proteins; D002454:Cell Differentiation; D002843:Chromatin / Q000737:chemistry / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D018076:DNA, Complementary / Q000235:genetics; D004847:Epithelial Cells / Q000737:chemistry / Q000166:cytology* / Q000378:metabolism; D004848:Epithelium / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007399:Interphase; D042361:Mammary Glands, Human / Q000737:chemistry / Q000166:cytology* / Q000378:metabolism; D034521:Nuclear Matrix-Associated Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D010455:Peptides / Q000737:chemistry / Q000235:genetics
D034961:Antigens, Nuclear; D018797:Cell Cycle Proteins; D002843:Chromatin; D018076:DNA, Complementary; C050045:NUMA1 protein, human; D034521:Nuclear Matrix-Associated Proteins; D010455:Peptides; D004247:DNA