Macrohistone Variants Preserve Cell Identity by Preventing the Gain of H3K4me2 during Reprogramming to Pluripotency

Transcription-factor-induced reprogramming of somatic cells to pluripotency is a very inefficient process, probably due to the existence of important epigenetic barriers that are imposed during differentiation and that contribute to preserving cell identity. In an effort to decipher the molecular nature of these barriers, we followed a genome-wide approach, in which we identified macrohistone variants (macroH2A) as highly expressed in human somatic cells but downregulated after reprogramming to pluripotency, as well as strongly induced during differentiation. Knockdown of macrohistone variants in human keratinocytes increased the efficiency of reprogramming to pluripotency, whereas overexpression had opposite effects. Genome-wide occupancy profiles show that in human keratinocytes, macroH2A.1 preferentially occupies genes that are expressed at low levels and are marked with H3K27me3, including pluripotency-related genes and bivalent developmental regulators. The presence of macroH2A.1 at these genes prevents the regain of H3K4me2 during reprogramming, imposing an additional layer of repression that preserves cell identity

Additional file 1: Figure S1. of Identification of resistant germplasm containing novel resistance genes at or tightly linked to the Pi2/9 locus conferring broad-spectrum resistance against rice blast

PCR amplification results of the 30 IRBLs and five rice cultivars using primer pair Pi2/9-DF1/DR1 (Pi2/9-RH). LTH, Lijiangxintuanheigu. IRBL, IRRI-bred blast-resistant lines. Figure S2. PCR amplification results of the 26 candidate resistant accessions using primer pair Pi2/9-DF1/DR1 (Pi2/9-RH). CO39 was used as a negative control while the Pi2 introgression line (IRBLz5-CA) was used as a positive control. Figure S3. Disease reaction of introgression line IR126183 (Pi2/9-A42) inoculated with the isolates 9244–3, M015–6 and 9482–1-3. R, resistance; PR, partial resistance; S, susceptibility; “+” indicates the PCR result is positive by Pi2/9-DF1/R1. Figure S4. Methods used for bioinformatics analysis of Pi2 and Nbs2-Pi2 alleles in 3K genomes. (PPTX 595 kb