TADs enriched in histone H1.2 strongly overlap with the B compartment, inaccessible chromatin, and AT‐rich Giemsa bands

Abstract

An epigenetic characterization of Giemsa bands (G bands) revealed their utility as epigenetic units to investigate the differential distribution of linker histones. GC content is a strong driver in histone H1 distribution: H1X is enriched at high GC bands and H1.2 is abundant at low GC, compacted bands. Hi‐C analysis showed that TADs with a high H1.2/H1X ratio strongly overlap with B compartment, inaccessible chromatin and low‐GC bands.

Coordinated changes in gene expression, H1 variant distribution and genome 3D conformation in response to H1 depletion

“…We calculated the abundance of each H1 within the G bands to compare its distribution upon H1 KD. In the absence of Dox, H1.2 was seen enriched towards low GC (Gpos100/Gneg4, repressed) bands, and H1X was enriched at high GC (Gpos25/Gneg1, active) bands, as expected from previous studies (18, 20). Besides, H1.4 was also enriched at high GC bands, whereas H1.5 and H1.0 were enriched towards low GC bands (Figure 1C).…”

“…For that, genome compartmentalization methods could ease comprehension of the data. Our recent studies support that Giemsa bands (G bands) are useful as epigenetic units to investigate the differential distribution of linker histones (20). When evaluating H1 variants abundance at G bands, several epigenetic features are also recapitulated and their correlation with GC content, transcription factors binding, chromatin accessibility or topology, among others, can be inferred.…”

“…Altogether, our results support H1 variants heterogeneity as well as their key role in the topological organization of the genome that has consequences on gene expression programs. 2/H1X ratio and a great overlap with low GC Giemsa bands, while the opposite occurs for A compartment (20). H1 variants were differentially distributed along the genome and two profiles could be distinguished in T47D breast cancer cells: H1.2, H1.5 and H1.0 co-localized at low GC regions whereas H1.4 and H1X occupied high GC regions.…”

“…This is, to our knowledge, the first time that so many endogenous variants have been profiled in a mammalian cell. In previous studies, we mapped endogenous H1.2 and H1X, demonstrating that they have different distributions across the genome (13,18,20). On the one side, H1.2 was enriched within intergenic, low gene expression regions and lamina-associated domains (LADs).…”

“…We have previously shown that quantification of the average abundance of each H1 variant input-subtracted ChIP-seq signal at cytobands (G bands) is an efficient method to compare their distribution (20). G bands were classified as G positive (Gpos25 to Gpos100, according to its intensity upon Giemsa staining), and G negative (unstained), which were further divided into four groups according to their GC content (Gneg1 to Gneg4, from high to low GC content) ( Figure 1C).…”