Epigenetic engineering shows H3K4me2 is required for HJURP targeting and CENP-A assembly on a synthetic human kinetochore

Kinetochores assemble on distinct 'centrochromatin' containing the histone H3 variant CENP-A and interspersed nucleosomes dimethylated on H3K4 (H3K4me2). Little is known about how the chromatin environment at active centromeres governs centromeric structure and function. Here, we report that centrochromatin resembles K4-K36 domains found in the body of some actively transcribed housekeeping genes. By tethering the lysine-specific demethylase 1 (LSD1), we specifically depleted H3K4me2, a modification thought to have a role in transcriptional memory, from the kinetochore of a synthetic human artificial chromosome (HAC). H3K4me2 depletion caused kinetochores to suffer a rapid loss of transcription of the underlying α-satellite DNA and to no longer efficiently recruit HJURP, the CENP-A chaperone. Kinetochores depleted of H3K4me2 remained functional in the short term, but were defective in incorporation of CENP-A, and were gradually inactivated. Our data provide a functional link between the centromeric chromatin, α-satellite transcription, maintenance of CENP-A levels and kinetochore stability.

1888 University of Michigan Football Team

1889 University of Michigan Football Team

1890 University of Michigan Football Team

1890 UM Football team

Back Row: Thomas L. McKean, Clark J. Sutherland, Tom Chadbourne, David Trainer, Horace Prettyman, David McMoran

3rd Row: Sam Sherman, Lawrence Grosh, Capt. William .C. Malley, mngr. George Codd, James E.. Duffy

2nd Row: George Jewett,

Front Row: George Dygert, George Jewett, George Holden, Roger Sherman

Scio Township and Ann Arbor Township (Mich.) residences and business, ca. 1874

Left to right: Res. of J.T. Sullivan Esq., Sec. 27, Scio Tp., Mich.; Res. of Wm. C. Foster, Sec. 26, Scio Tp. Mich.; Res. of L.C. Risdon, Dealer in Hardware, No. 81 South Main St., Ann Arbor, Mich.; Res. of Dr. D.B. Kellogg, Ann Arbor, Mich.; Ann Arbor, Mich.; Res. of David Mowerson, Sec. 14, Ann Arbor Tp. Mich. Publication information: Chicago, Ill. : Everts & Stewart, 1874

South College

South Wing, also called South College, built in 1849; demolished in 1950. Male person in image. On verso: Evidently the old South Wing of "South College" taken prior to 1871. The view, in the opinion of William C. Hood, who studied the shadows, from the northwest. Wm. Shaw, 11/30/37

Procedures for estimating dry weather pollutant deposition in sewerage systems /

Mode of access: Internet.

Comparison of numerical and physical hydraulic models, Masonboro Inlet, North Carolina : Appendix 1, fixed-bed hydraulic model results /

"June 1977."

Supplementary tests of Masonboro Inlet fixed-bed model : hydraulic model investigation /

"General investigation of tidal inlets; a program of research conducted jointly by U.S. Army Coastal Engineering Research Center, Fort Belvoir, Virginia [and] U.S. Army Engineer Waterways Experiment Station, Vicksburg, Mississippi."

The government of New Hampshire,

"Primary ballots" (2 folded leaves), "Official ballot" (folded leaf), "Map of New Hampshire" (folded leaf), "Chart of New Hampshire government" (folded leaf), "New Hampshire state flag" (plate) in pocket.

Studies in Longfellow. Outlines for schools, conversation classes, and home study.

Mode of access: Internet.

Los Angeles and Long Beach Harbors model study : numerical analysis of tidal circulation for the 2020 Master Plan /

"June 1984."