Molecular Text 4.5

·         Eukaryotes also contain a few __ that assemble into __, which are present in small amounts and are not as __
·         Major histones are made mostly during the __ and assembled into __ just behind the __. 

·         In contrast, most histone variants are synthesized throughout __.
o   They are often inserted into __, which requires a __ catalyzed by the __
§  These __ contain subunits that cause them to do what? As a result, each histone variant is inserted into chromatin in a highly selective manner. 

·         Thousands of modification combos can exist; and there is further diversity created by __that contain __. These combos have specific meaning because they determine what?

o   Small protein modules bind to specific marks, recognizing particular __. These module act in concert with other modules as part of a __, so as to allow particular combinations of markings on chromatin to do what? 

·         The marks on nucleosomes due to __ are dynamic, being constantly removed and added at rates dependent on __
o   Because the histone tails extend outward from the __ and are likely to be accessible even in __, they would seem to provide a suitable format for creating marks in a form that can be readily altered as a cell’s needs change

·         __ requires that some modified forms of chromatin have the ability to __
·         The enzymes that modify (or remove modifications form) the histones in nucleosomes are part of __. They can initially be brought to a particular region of chromatin by one of the __

o   But after a modifying enzyme __, events that resemble a chain reaction can ensue.
§  The __ works in concert with a __ located in the same protein complex.
§  The second proteoin contains a __ that recognizes the mark and binds tightly to the newly modified __, positioning its attached writer enzyme near an adjacent nucleosome

·         Through many such __, the __ can carry the __ along the DNA—spreading the mark in a hand-over-hand manner along the chromosome
·         Both __ are part of a protein complex that is likely to contain multiple __, and to require multiple marks on the nucleosome to spread
o   Moreover, many of these __ also contain an __, and the reader, writer, and remodeling proteins work in concert to either __  or _as the reader moves progressively along the __

·         What prevents a cacophony of confusing cross-talk between adjacent chromatin domains of different structure and function?

§  Ex: HS4 domain contains the __ from an adjacent region of silenced, condensed chromatin. If this sequence is deleted, the __ is what, which does what, and it spreads to a different extent in different cells, causing a pattern of __
·         This invasion has dire consequences: the globin genes are poorly expressed, and individuals who carry such a deletion have a severe form of anemia

·         The __ is often added to both ends of a gene that is inserted into a mammalian genome to do what?
o   It contains a cluster of __ for __
§  Since the __ is incompatible with the __, histone acetylases and deacetylases are logical for formation of __
·         Several other types of chromatin modifications can also protect genes from silencing

·         The presence of nucleosome carrying histone variants produces __ that are __
o   For example, each centromere is embedded in a stretch of special __ that persists throughout __, even though the __ occur only during mitosis. 

§  This chromatin contains a __, known as __, plus additional proteins that __ and __

·         The __in more complex organisms are considerably larger in those in budding yeasts; and, they consist of short, repeated DNA sequences, known as__ in humans. The same repeat sequences are also found at other (__) positions on chromosomes, indicating that they are __
New human centromeres (called __) have been observed to form spontaneously on __. Some of these new positions were originally __and lack __ altogether

·         Centromeres in complex organisms are defined by an __, instead of by a __
o   The stretched chromosome fibers from centromeres have __, which allows the __ to fold so as to position the __ on the outside of the mitotic chromosome where they do what, which in turn do what?

·         It has been proposed that __ requires an initial seeding event, involving the formation of a specialized DNA-protein structure that contains __formed with the__
o   In humans, this seeding event happens more readily on arrays of __ than on other DNA sequence

§  The __ from each nucleosome on the parental DNA helix are directly inherited by the __ at a __
·         Once a set of __ has been assembled on a stretch of DNA, it is easy to understand how a __ could be generated in the same place on both daughter chromosomes following each round of cell division

·         The __ may provide an important evolutionary advantage. Chromosomes that evolve by breaking and rejoining events produce __.
o   Both the __ and their ability to be __ may occasionally allow newly formed chromosomes to be __, thereby facilitating the process of __

·         The formation and maintenance of centromeres is similar to the formation and maintenance of other regions of heterochromatin in that what?

Moreover, once formed, the structure seems to be __