Non-redundant functions of H2A.Z.1 and H2A.Z.2 in chromosome segregation and cell cycle progression

Abstract

SUMMARYH2A.Z is a H2A-type histone variant essential for many aspects of cell biology ranging from gene expression to genome stability. From deuterostomes, H2A.Z evolved into two paralogues H2A.Z.1 and H2A.Z.2 that differ by only three amino acids and are encoded by different genes (H2AFZ and H2AFV respectively). Despite the importance of this histone variant in development and cellular homeostasis, very little is known about the individual functions of each paralogue in mammals. Here we investigated the distinct roles of two paralogues in cell cycle regulation. Using a specific siRNA approach for each paralogue in human cells, we unveiled non-redundant functions for H2A.Z.1 and H2A.Z.2 in cell division: H2A.Z.1 regulates the expression of important cell cycle genes (including Myc and Ki-67) and its depletion leads to a G1 arrest, whereas H2A.Z.2 is essential for centromere integrity and function, thus playing a key role in chromosome segregation.

Transforming primary human hepatocytes into hepatocellular carcinoma with genetically defined factors

“…iHCC mimics the histological architecture, tumor serum marker profile, and gene expression characteristics of human HCC. However, Ki‐67, a marker of proliferation (Sales‐Gil et al , 2021), was highly expressed in iHCC, which is not common in primary human HCC, possibly indicating the aggressiveness of iHCC. To our knowledge, it is the first in vivo model of orthotopic transformation of human PHHs into HCC cells.…”

Histone variant H2A.Z modulates nucleosome dynamics to promote DNA accessibility

“…On another hand, the incorporation of H2A.Z may decrease but widen the barrier to transcription (13) and slow the rate of RNAPII pause release (14). In addition, many experimental studies reveal that H2A.Z can accumulate in facultative heterochromatin regions and areas of silenced genes (15,16) and could be involved in heterochromatin boundaries (17) and chromosome segregation (18), facilitate DNA doublestrand break repair (19), and cell cycle progression (20). The functional implications of H2A.Z can perhaps be revealed by studying its physicochemical properties, stability, and dynamics.…”