TY - JOUR

T1 - The large fraction of heterochromatin in Drosophila neurons is bound by both B-type lamin and HP1a

AU - Pindyurin, Alexey V.

AU - Ilyin, Artem A.

AU - Ivankin, Anton V.

AU - Tselebrovsky, Mikhail V.

AU - Nenasheva, Valentina V.

AU - Mikhaleva, Elena A.

AU - Pagie, Ludo

AU - van Steensel, Bas

AU - Shevelyov, Yuri Y.

N1 - Publisher Copyright: © 2018 The Author(s).

PY - 2018/11/1

Y1 - 2018/11/1

N2 - BACKGROUND: In most mammalian cell lines, chromatin located at the nuclear periphery is represented by condensed heterochromatin, as evidenced by microscopy observations and DamID mapping of lamina-associated domains (LADs) enriched in dimethylated Lys9 of histone H3 (H3K9me2). However, in Kc167 cell culture, the only Drosophilla cell type where LADs have previously been mapped, they are neither H3K9me2-enriched nor overlapped with the domains of heterochromatin protein 1a (HP1a). RESULTS: Here, using cell type-specific DamID we mapped genome-wide LADs, HP1a and Polycomb (Pc) domains from the central brain, Repo-positive glia, Elav-positive neurons and the fat body of Drosophila third instar larvae. Strikingly, contrary to Kc167 cells of embryonic origin, in neurons and, to a lesser extent, in glia and the fat body, HP1a domains appear to overlap strongly with LADs in both the chromosome arms and pericentromeric regions. Accordingly, centromeres reside closer to the nuclear lamina in neurons than in Kc167 cells. As expected, active gene promoters are mostly not present in LADs, HP1a and Pc domains. These domains are occupied by silent or weakly expressed genes with genes residing in the HP1a-bound LADs expressed at the lowest level. CONCLUSIONS: In various differentiated Drosophila cell types, we discovered the existence of peripheral heterochromatin, similar to that observed in mammals. Our findings support the model that peripheral heterochromatin matures enhancing the repression of unwanted genes as cells terminally differentiate.

AB - BACKGROUND: In most mammalian cell lines, chromatin located at the nuclear periphery is represented by condensed heterochromatin, as evidenced by microscopy observations and DamID mapping of lamina-associated domains (LADs) enriched in dimethylated Lys9 of histone H3 (H3K9me2). However, in Kc167 cell culture, the only Drosophilla cell type where LADs have previously been mapped, they are neither H3K9me2-enriched nor overlapped with the domains of heterochromatin protein 1a (HP1a). RESULTS: Here, using cell type-specific DamID we mapped genome-wide LADs, HP1a and Polycomb (Pc) domains from the central brain, Repo-positive glia, Elav-positive neurons and the fat body of Drosophila third instar larvae. Strikingly, contrary to Kc167 cells of embryonic origin, in neurons and, to a lesser extent, in glia and the fat body, HP1a domains appear to overlap strongly with LADs in both the chromosome arms and pericentromeric regions. Accordingly, centromeres reside closer to the nuclear lamina in neurons than in Kc167 cells. As expected, active gene promoters are mostly not present in LADs, HP1a and Pc domains. These domains are occupied by silent or weakly expressed genes with genes residing in the HP1a-bound LADs expressed at the lowest level. CONCLUSIONS: In various differentiated Drosophila cell types, we discovered the existence of peripheral heterochromatin, similar to that observed in mammals. Our findings support the model that peripheral heterochromatin matures enhancing the repression of unwanted genes as cells terminally differentiate.

KW - B-type lamin

KW - Drosophila

KW - Heterochromatin

KW - HP1

KW - Lamina-associated domains

KW - Polycomb

KW - Cell Line

KW - Heterochromatin/genetics

KW - Drosophila Proteins/genetics

KW - Chromosomal Proteins, Non-Histone/genetics

KW - Histones/metabolism

KW - Animals

KW - Neurons/metabolism

KW - Protein Binding

KW - Lamin Type B/genetics

KW - CHROMATIN-STRUCTURE

KW - PROTEIN-1 HP1

KW - HISTONE H3

KW - GENE-EXPRESSION

KW - LYSINE 9

KW - STEM-CELLS

KW - NUCLEAR LAMINA

KW - GENOME

KW - BINDING

KW - MELANOGASTER

UR - http://www.scopus.com/inward/record.url?scp=85055915604&partnerID=8YFLogxK

U2 - 10.1186/s13072-018-0235-8

DO - 10.1186/s13072-018-0235-8

M3 - Article

C2 - 30384843

AN - SCOPUS:85055915604

VL - 11

SP - 65

JO - Epigenetics and Chromatin

JF - Epigenetics and Chromatin

SN - 1756-8935

IS - 1

M1 - 65

ER -