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NuMA Influences Higher Order Chromatin Organization in Human Mammary Epithelium

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Journal Mol Biol Cell
Date 2006 Nov 17
PMID 17108325
Citations 34
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Abstract

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.

Citing Articles

The Nuclear Mitotic Apparatus (NuMA) Protein: A Key Player for Nuclear Formation, Spindle Assembly, and Spindle Positioning.

Kiyomitsu T, Boerner S Front Cell Dev Biol. 2021; 9:653801.

PMID: 33869212 PMC: 8047419. DOI: 10.3389/fcell.2021.653801.


3D Cell Culture for the Study of Microenvironment-Mediated Mechanostimuli to the Cell Nucleus: An Important Step for Cancer Research.

Chhetri A, Rispoli J, Lelievre S Front Mol Biosci. 2021; 8:628386.

PMID: 33644116 PMC: 7902798. DOI: 10.3389/fmolb.2021.628386.


The mitotic protein NuMA plays a spindle-independent role in nuclear formation and mechanics.

Serra-Marques A, Houtekamer R, Hintzen D, Canty J, Yildiz A, Dumont S J Cell Biol. 2020; 219(12).

PMID: 33044554 PMC: 7555356. DOI: 10.1083/jcb.202004202.


Special issue: Nuclear architecture and chromatin motions in the DNA damage response.

Locatelli M, Vidi P Mutat Res. 2020; 821:111721.

PMID: 32846362 PMC: 9581968. DOI: 10.1016/j.mrfmmm.2020.111721.


NuMA interaction with chromatin is vital for proper chromosome decondensation at the mitotic exit.

Rajeevan A, Keshri R, Kapoor S, Kotak S Mol Biol Cell. 2020; 31(22):2437-2451.

PMID: 32845810 PMC: 7851854. DOI: 10.1091/mbc.E20-06-0415.


References
1.
Szekely L, Kiss C, Mattsson K, Kashuba E, Pokrovskaja K, Juhasz A . Human herpesvirus-8-encoded LNA-1 accumulates in heterochromatin- associated nuclear bodies. J Gen Virol. 1999; 80 ( Pt 11):2889-2900. DOI: 10.1099/0022-1317-80-11-2889. View

2.
Blaschke R, Howlett A, Desprez P, Petersen O, Bissell M . Cell differentiation by extracellular matrix components. Methods Enzymol. 1994; 245:535-56. DOI: 10.1016/0076-6879(94)45027-7. View

3.
Taimen P, Viljamaa M, Kallajoki M . Preferential expression of NuMA in the nuclei of proliferating cells. Exp Cell Res. 2000; 256(1):140-9. DOI: 10.1006/excr.2000.4799. View

4.
Merdes A, Heald R, Samejima K, Earnshaw W, Cleveland D . Formation of spindle poles by dynein/dynactin-dependent transport of NuMA. J Cell Biol. 2000; 149(4):851-62. PMC: 2174573. DOI: 10.1083/jcb.149.4.851. View

5.
Logdberg L, Akerstrom B, Badve S . Tissue distribution of the lipocalin alpha-1 microglobulin in the developing human fetus. J Histochem Cytochem. 2000; 48(11):1545-52. DOI: 10.1177/002215540004801111. View